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M .M & 414 TRADE SECRET Study Title H-24768: Developmental Toxicity Study in Rats Laboratory Project ID: DuPont-6515 DuPont-6515 T e s t G u i d e l i n e s : U.S. EPA Health Effects Test Guidelines OPPTS 870.3700 Prenatal Developmental Toxicity Study OECD Guidelines for the Testing o f Chemicals Section 4, No. 414 A u t h o r : Susan M. Munley, M.A. S t u d y C o m p l e t e d o n : February 25, 2002 P e r f o r m i n g L a b o r a t o r y : E.I. du Pont de Nemours and Company Haskell Laboratory for Toxicology and Industrial Medicine Elkton Road, P.O. Box 50 Newark, Delaware 19714-0050 Page 1 of 165 C om pany S anitized. D o e s not contain TSCA CB1 H-24768: Developmental Toxicity Study in Rats DuPont-6515 GOOD LABORATORY PRACTICE COMPLIANCE STATEMENT This study was conducted in compliance with U.S. EPA TSCA (40 CFR part 792) Good Laboratory Practice Standards, which are consistent with the OECD Principles o f Good Laboratory Practice (as revised in 1997) published in ENV/MC/CHEM(98)17, except for the item documented below. The item listed does not impact the validity o f the study. The bulk test substance characterization and stability analyses were performed at DuPont Regional Analytical Services (RAS), a non-GLP laboratory. These analyses were in compliance with regulatory guidelines. None of the aforementioned analyses were performed under Good Laboratory Practice Standards; however, the analyses were conducted in compliance with IS09002 regulations. All o f the analyses are considered valid and sufficient for the purposes o f this study. Applicant / Sponsor: E. I. du Pont de Nemours and Company Wilmington, Delaware 19898 U.S.A. Applicant / Sponsor Research Scientist DuPont Representative Date Date -2 - Company Sanitized. Does not contain TSCA CBI H-24768: Developmental Toxicity Study in Rats QUALITY ASSURANCE STATEMENT Haskell Sample Number(s): 24768 Dates of Inspections: Protocol: May 1,2001, Jan. 14, 2002 Conduct: May 4,9, 2001, July 11,19, 2001 Records, Reports: Jan. 15-18,21-24,28, 2002 Dates Findings Reported to: Study Director: Jan. 28,29, 2002 Management: Jan. 28, 2002, Feb. 20, 2002 DuPont-6515 Reported by: I f - Fr i tO'tr Date -3 Company Sanitized. Does not contain TSCA CBi H-24768: Developmental Toxicity Study in Rats DuPont-6515 CERTIFICATION We, the undersigned, declare that this report provides an accurate evaluation o f data obtained from this study. Approved by: Robert M. Parker, Ph.D., D.AJB.T. Director Developmental and Reproductive Toxicology And Neurobehavioral Toxicology Issued by Study Director: Date Date -4 Company Sanitized. Does not contain TRCft CBI H-24768: Developmental Toxicity Study in Rats DuPont-6515 TABLE OF CONTENTS Page GOOD LABORATORY PRACTICE COMPLIANCE STATEM ENT......................................2 QUALITY ASSURANCE STATEM ENT..........................................................................................3 C E R T I F I C A T I O N ................................................................................................................................... 4 STUDY INFORMATION...................................................................................................................... 7 STUDY PERSONNEL............................................................................................................................ 8 SUM M ARY...............................................................................................................................................9 O BJECTIV E.......................................................................................................................................... 10 MATERIALS AND M ETHODS........................................................................................................ 10 A. Test G uidelines........................................................................................................................... 10 B. Test Substance.............................................................................................................................10 C. Test Species......................................................................... 10 D. Animal Husbandry...................................................................................................................... 11 1. Housing............................................................................................................................................................11 2. Feed and W ater............................................................................................................................................... 11 3. Identification....................................................................................................................................................11 4. Health Monitoring Program........................................................................................................................... 11 E. Quarantine and Pretest Period....................................................................................................12 F. Study Design................................................................................................................................12 G. Selection o f Dose Levels............................................................................................................ 12 H. Randomization............................................................................ 13 I. Preparation, Administration, and Analysis of Test Suspensions.......................................... 13 J. Animal Euthanasia...................................................................................................................... 13 K. Parameters to be Studied............................................................................................................ 13 1. In-life Observations of Females................................................................................................................... 13 2. Postmortem Observations of Females Surviving to Scheduled Euthanasia............................................... 13 3. Fetuses of Females Surviving to Scheduled Euthanasia.............................................................................. 14 L. Control o f Bias.............................................................................................................................14 M. Statistical Analyses..................................................................................................................... 15 RESULTS AND DISCUSSION.......................................................................................................... 16 A. Maternal Findings...................................................................................................................... 16 1. Mortality.......................................................................................................................................................... 16 2. Body Weights...................................................................................................................................................16 3. Body Weight Changes................................................................... 16 4. Food Consumption.......................................................................................................................................... 17 -5 Company Sanitized. Does no! contain trca CBI H-24768: Developmental Toxicity Study in Rats DuPont-6515 5. Clinical Observations.... ............................................................... 17 6. Postmortem Findings......................................................................................................................................17 B. Fetal Findings.............................................................................................................................. 17 1. Mortality..........................................................................................................................................................17 2. Body Weight................................................................................................................................................... 18 3. Malformations................................................................................................................................................. 18 4. Variations.........................................................................................................................................................18 C O N C L U S IO N S .................................................................................................................................... 19 RECORDS AND SAMPLE STORAGE...........................................................................................19 R E F E R E N C E S ....................................................................................................................................... 20 T A B L E S ...................................................................................................................................................21 TABLE 1 MEAN MATERNAL BODY WEIGHTS........................................................................................................ 22 TABLE 2 MEAN MATERNAL BODY WEIGHT CHANGES......................................................................................25 TABLE 3 MEAN MATERNAL FOOD CONSUMPTION..............................................................................................27 TABLE 4 CLINICAL OBSERVATIONS......................................................................................................................... 29 TABLE 5 REPRODUCTIVE OUTCOME................................................... 30 TABLE 6 INCIDENCE OF FETAL MALFORMATIONS..............................................................................................31 TABLE 7 INCIDENCE OF FETAL VARIATIONS........................................................................................................ 33 APPENDICES....................................................................................................................................... 36 APPENDIX A INDIVIDUAL BODY WEIGHTS..... .......................................................................................................37 APPENDIX B INDIVIDUAL BODY WEIGHT CHANGES..........................................................................................51 APPENDIX C INDIVIDUAL FOOD CONSUMPTION..................................................... 61 APPENDIX D INDIVIDUAL CLINICAL OBSERVATIONS....................................................................................... 71 APPENDIX E GROSS POSTMORTEM FINDINGS...................................................................................................... 94 APPENDIX F INDIVIDUAL REPRODUCTIVE DATA.............................................................................................. 100 APPENDIX G INDIVIDUAL FETAL WEIGHTS AND ALTERATIONS................................................................. 106 APPENDIX H ANALYTICAL REPORT................................................................................................ 154 -6- Company Sanitized. Does not contain t s c a CBl H-24768: Developmental Toxicity Study in Rats STUDY INFORMATION DuPont-6515 Haskell Number: 24768 Physical Characteristics: Tan to light brown paste Stability: The test substance appeared to be stable under the conditions o f the study; no evidence of instability was observed. Sponsor: E. I. du Pont de Nemours and Company Wilmington, Delaware 19898 U.S.A. Study Initiated/Completed: May 4, 2001 / (see report cover page) In-Life Initiated/Completed: May 6, 2001 / August 23, 2001 -7Company Sanitized. Does not contain TSCA C8 H-24768: Developmental Toxicity Study in Rats STUDY PERSONNEL Study Director: Susan M. Munley, M.A. Management: Robert M. Parker, Ph.D., D.A.B.T. Primary Technician: Kellie Mcllhatton Toxicology Report Preparation: Mary K. LaRoe Laboratory Veterinarian: William Singleton, D.V.M., A.C.L.A.M. DuPont-6515 -8 Company Sanitized. Does not contain TSCA CB! H-24768: Developmental Toxicity Study in Rats DuPont-6515 SUMMARY Groups of 22 female Crl:CD(SD)IGS BR time-mated rats were administered suspensions o f H-24768 in water once daily by gavage over days 6-20 o f gestation (G) at dose levels o f 0,50, 100, or 400 mg/kg/day. During the dosing period, body weight, food consumption, and clinical observation data were collected daily. On day 21G, all dams were euthanized and examined for gross external and visceral alterations. The uteri were removed, weighed, and dissected. The uterine contents were examined; the fetuses were removed and weighed, sexed, and examined for external, visceral, head, and skeletal alterations. Maternal toxicity was evident at 100 and 400 mg/kg/day as significant reductions in maternal body weight, weight change, and food consumption. The magnitude o f the quantitative maternal changes at 400 mg/kg/day was marked. Increased clinical signs o f toxicity accompanied the weight and food consumption reductions at 400 mg/kg/day. There were compound-related effects on maternal weight, weight change, and food consumption at 50 mg/kg/day but these changes were generally minimal and transient and as such, were not considered adverse. Developmental toxicity was evident only at 400 mg/kg/day as significantly reduced mean fetal weight and increased fetal variations (delayed skull bone ossification and increased supernumerary ribs). There was no evidence of developmental toxicity at 50 or 100 mg/kg/day. There were no compound-related fetal malformations at any level tested. Under the conditions o f this study, maternal toxicity evident as reduced body weight and food consumption was observed at > 100 mg/kg/day. Non-adverse changes in dams occurred at 50 mg/kg/day and thus, the maternal no-observed-effect level (NOEL) was considered 50 mg/kg/day. Developmental toxicity was evident at 400 mg/kg/day as reduced fetal weight and increased fetal variations. The NOEL for developmental toxicity was considered 100 mg/kg/day. a The NOEL for this study is defined as the highest dose at which adverse effects attributable to the test substance were not detected. Thus, for this study, the NOEL is equivalent to the NOEL as defined by the U.S. EPA (1985) and to the no-observed-adverse-effect level (NOAEL) as defined by the European Union (1994). -9 Company Sanitized. Does not contain t so a CBI H-24768: Developmental Toxicity Study in Rats DuPont-6515 OBJECTIVE The purpose of this study was to evaluate the potential maternal and developmental toxicity of H-24768 in rats. MATERIALS AND METHODS A. Test Guidelines The study design complies with following test guidelines: United States Environmental Protection Agency (EPA), Office of Prevention, Pesticides, and Toxic Substances (OPPTS) Health Effects Test Guidelines, OPPTS 870.3700 Prenatal Developmental Toxicity Study (1998). Organisation for Economic Cooperation and Development. Guidelines for Testing o f Chemicals, Section 4 (No. 414). Paris, France (1981). B. Test Substance H-24768 was supplied by the sponsor, the DuPont Chemical Solutions Enterprise (DCSE), E. I. Du Pont de Nemours and Company, Newark, Delaware. H-24768 is a paste. It was assigned Haskell Laboratory Number 24768. The sponsor was responsible for the characterization and stability o f the test substance. Test substance analyses were conducted by DuPont Regional Analytical Services (RAS), Jackson Laboratories, Deepwater, New Jersey. A reserve sample of the test substance was collected and retained by DuPont Haskell Laboratory. C. Test Species The Crl:CD(SD)IGS BR rat was selected for this study because it is a preferred species for developmental toxicity testing as recommended by the guidelines. The Crl:CD(SD)IGS BR strain was chosen because extensive background information is available from the literature, the supplier, and previous studies with other compounds at Haskell Laboratory. This strain is also considered suitable relative to hardiness and incidence o f spontaneous disease. - 10Company Sanitized. Does not contain TSCA CB H-24768: Developmental Toxicity Study in Rats DuPont-6515 Eighty-eight nulliparous, time-mated females, were received on May 3, 2001 (66 females) and May 4,2001 (22 females) from Charles River Laboratories, Inc., Raleigh, North Carolina. Body weights on the day the rats were mated, day 0 of gestation (day 0G), were supplied by the vendor. The rats for this study were at either 1, 2, or 3 days o f gestation upon arrival. D. Animal Husbandry 1. Housing Animal rooms were maintained at an acceptable temperature o f 20-26C (targeted at 23 C) and a targeted relative humidity o f 50% 10%. Animal rooms were artificially illuminated (fluorescent light) on a 12-hour light/dark cycle (approximately 0600-1800 hours). Animals were housed individually in suspended, wire-mesh, stainless steel cages. Nesting material was not provided because the dams were euthanized prior to parturition. 2. Feed and Water PMI Nutrition International, Inc. Certified Rodent LabDiet 5002 (formerly known as Purina Certified Rodent Chow) was available ad libitum. Water from the United Water Delaware was available ad libitum. 3. Identification Each animal was assigned a unique number and was identified with an AVID Microchip implant by the supplier prior to shipping. Upon receipt, each animal was assigned a unique Haskell animal number. Both the Haskell animal number and the AVID Microchip implant number or tail mark were recorded on each cage card. A master list of unique Haskell animal numbers and corresponding unique AVID Microchip implant numbers is maintained with the study records. 4. Health Monitoring Program As specified in the Haskell Laboratory animal health and environmental monitoring program, the following procedures are performed periodically to ensure that contaminant levels are below those that would be expected to impact the scientific integrity o f the study: Water samples are analyzed for total bacterial counts, and the presence o f coliforms, lead, and other contaminants. Feed samples are analyzed for total bacterial, spore and fungal counts. Samples from freshly washed cages and cage racks are analyzed to ensure adequate sanitation by the cagewashers. Certified animal feed is used, guaranteed by the manufacturer to meet specified nutritional requirements and not to exceed stated maximum concentrations of key contaminants, including specified heavy metals, aflatoxin, chlorinated hydrocarbons, and organophosphates. The -11 Company Sanitized. Does not confsUn CBI H-24768: Developmental Toxicity Study in Rats DuPont-6515 presence of these contaminants below the maximum concentration stated by the manufacturer would not be expected to impact the integrity o f the study. The animal health and environmental monitoring program is administered by the attending laboratory animal veterinarian Evaluation of these data did not indicate any conditions that affected the validity o f the study. E. Quarantine and Pretest Period Rats were quarantined according to procedures outlined in Haskell Laboratory SOP LA003-P, and then released for the study upon approval o f the Laboratory Animal Veterinarian designee. F. Study Design The experimental design is shown below: Group Dose3 (mg/kg/day) Suspension Concentration (me/mL) Time-Mated Females I 0b 0 22 II 50 5 III 100 10 IV 400 40 22 22 22 a H-24768, administered by oral gavage, on days 6-20 of gestation (G), at a dose volume of 10 mL/kg. b Vehicle (deionized water) G. Selection o f Dose Levels The dose levels for the current study were based on results o f a rat pilot developmental toxicity study with the test substance.(1) For the pilot study, groups o f 8 time-mated female Crl:CD(SD)IGS BR rats were administered suspensions o f the test substance once daily by gavage over days 6-20 o f gestation (G) at 0, 50, 100, 400, and 700 mg/kg/day. Maternal toxicity consisting o f significant reductions in maternal body weight, weight gain, and food consumption and increased clinical signs o f toxicity occurred at >_400 mg/kg/day. Developmental toxicity evident as significantly reduced mean fetal weight occurred at >.400 mg/kg/day. There was no evidence o f either maternal or developmental toxicity at < 100 mg/kg/day. Based on these results, the dose levels listed above were selected for the current study. - 12- Sgm pany Sanitized. Does not contain TSCA CBf H-24768: Developmental Toxicity Study in Rats DuPont-6515 H. Randomization Dams were assigned to lots according to their gestation day. Then, they were ranked within their respective lots on the basis of day OG body weights and assigned to control and experimental groups by random sampling from the ranked list. The distribution resulted in mean body weights for all groups that were not statistically different (p > 0.05). I. Preparation, Administration, and Analysis of Test Suspensions Suspensions o f the test substance in the vehicle (water) were prepared 2 or 3 times per week, and stored refrigerated until used. The method of mixing the test material with the vehicle was documented in the study records. The dosing suspensions were administered by gavage because the oral route is the route that is recommended by regulatory agencies for this type o f study. The volume administered (10 mL/kg) was based on the most recent body weight. Samples of each test suspension were taken three times during the study, near the beginning, middle, and end o f the dosing period. Analyses of the first sampling addressed homogeneity, concentration, and stability. For the second and third samplings, analyses addressed concentration. Samples were submitted, shortly after preparation to the Analytical Chemistry Group at Haskell Laboratory. The methods and results o f these analyses are presented in Appendix H. J. Animal Euthanasia Females were euthanized by carbon dioxide asphyxiation. Fetuses were decapitated before proceeding with visceral examinations; those to be viscerally examined without decapitation were injected with sodium pentobarbital. All other fetuses also were injected with sodium pentobarbital before fixation. K. Parameters to be Studied 1. In-life Observations of Females Body weights were recorded at least twice prior to dosing to provide data for quarantine release, and on days 6-21G. Food consumption was measured on days 4, 6, 8,10, 12, 14, 16, 18, 20, and 21G. Clinical signs were recorded at least twice prior to dosing to provide data for quarantine release; signs were recorded once daily on days 4, 5, and 21G and twice daily on days 6-20G. 2. Postmortem Observations of Females Surviving to Scheduled Euthanasia The abdominal and thoracic viscera were examined grossly immediately after euthanasia on day 21G. The intact and the empty uterus o f each dam having at least one viable fetus was weighed -13 - Sanitized. D o e s not contain t q ^ a CBf K pinpany S an itized . D o e s not H-24768: Developmental Toxicity Study in Rats DuPont-6515 to permit calculation o f maternal body weight adjusted to exclude the products o f conception. The corpora lutea count for each ovary of females with viable fetuses was recorded. For each female with visible implantation sites, the types o f implants (live and dead fetuses, and resorptions) and their relative positions were recorded. The uterus of each apparently "nonpregnant" female was stained with ammonium sulfide to detect very early resorptions. 3. Fetuses of Females Surviving to Scheduled Euthanasia For each fetus, the following parameters were recorded: identification number, intrauterine location, sex, and body weight. The external alterations detected for each live fetus were also recorded. For each litter, the first live fetus and every other live fetus thereafter were examined for visceral alterations. Retarded renal development was classified using the scheme o f Woo and Hoar. In addition, all live fetuses with malformations visible at external examination were examined for soft tissue alterations; decapitation o f these fetuses was at the discretion o f the study director or a designee. After fixation in Bouin's fixative, the heads o f decapitated fetuses were examined and alterations were recorded. Examinations were based on the method of Barrow and Taylor. After alcohol fixation, the alizarin-stained skeletons were examined and skeletal alterations were recorded for all live fetuses, excluding the fetal heads fixed in Bouin's fixative. L. Control of Bias In addition to random assignment to groups, all females were coded before scheduled euthanasia and remained coded during the collection of postmortem and fetal data. Com pany Sanitized. D oes not contain TSCA Ciu - 14- H-24768: Developmental Toxicity Study in Rats DuPont-6515 M. Statistical Analyses Sequential two-tailed trend testing(6) was applied to the data for each parameter as tabulated below. If a significant dose-response was detected, data from the top dose group was excluded and the test repeated until no significant trend was detected. For litter parameters, the proportion of affected fetuses per litter or the litter mean was used as the experimental unit for statistical evaluation.(7) The level o f significance selected was p < 0.05. Where the data were tied and the standard large sample version o f Jonckheere's test was not applicable, exact p values were calculated using permutation methodology.(8) Parameter Maternal weight Maternal weight changes Maternal food consumption Live fetuses Dead fetuses Resorptions Implantations Incidence o f fetal alterations Incidence o f pregnancy Clinical observations Maternal mortality Females with total resorptions Early deliveries Fetal weight (Covariates: litter size, sex ratio) Sex ratio (Covariate: litter size) Trend Test Linear contrast o f means(9) Jonckheere's test(10) Cochran-Armitage test(9) Linear contrast o f least square means(1,) cv t\0,\co*ixav't' JO - 15- H-24768: Developmental Toxicity Study in Rats DuPont-6515 RESULTS AND DISCUSSION A. Maternal Findings 1. Mortality There was no compound-related mortality at any level tested; all rats on study survived to scheduled sacrifice. 2. Body Weights (Table 1, Appendix A) There were compound-related reductions in mean maternal body weights at 100 and 400 mg/kg/day; at these dose levels, mean body weight was significantly reduced beginning on day 7G and the reduction persisted until the end o f the study. At 400 mg/kg/day, mean weights were reduced > 10% when compared with control group values beginning on day 8G and final body weights were reduced 16% when compared with control group values (using either the absolute final weight or the final weight adjusted for the weight o f the products o f conception). At 100 mg/kg/day, mean weights were reduced 5%-7% when compared with control group values starting on day 7G and persisting until the end o f the study. At 50 mg/kg/day, there were minimal, statistically significant reductions in mean maternal weights on days 9 and 10G. These reductions were not considered adverse because they were minimal in magnitude (reduced 2%-3% when compared with control group values), transient in nature, and had no impact on final body weight. 3. Body Weight Changes (Table 2, Appendix B) There were compound-related reductions in mean maternal weight gains (including body weight losses at the beginning of dosing) at 100 and 400 mg/kg/day. At these levels, mean weight gain was significantly reduced over days 6-8 and 8-10G. At 400 mg/kg/day, mean weight gain over days 12-14,16-18, and 20-21G was also significantly reduced. As a result, the mean weight gain calculated over days 6-21G was significantly reduced at 100 and 400 mg/kg/day. Mean weight gain was reduced 13/30% and 44/98% when compared with control group values (using the absolute/adjusted final weight to calculate the gain) at 100 and 400 mg/kg/day, respectively. At 50 mg/kg/day, there was a slight mean weight loss at the beginning o f dosing (days 6-8G) that was statistically significant. Thereafter, mean weight gain at 50 mg/kg/day was generally comparable to the control group. However, because o f the initial weight loss, overall weight gain was reduced (reduced 6/14% when compared with control group values); the overall gain calculated using the adjusted final weight was significantly lower. Because these reductions had no appreciable impact on final weight and because they were transient, they were not considered adverse. nia'0. t S CNC po1 - 16- SaTM COf1lip1'* H-24768: Developmental Toxicity Study in Rats DuPont-6515 4. Food Consumption (Table 3, Appendix C) There were compound-related reductions in mean food consumption at 100 and 400 mg/kg/day. At 400 mg/kg/day, mean food consumption was significantly lower beginning over days 6-8G and persisting until the end o f the study. At 100 mg/kg/day, mean food consumption was significantly lower over days 6-8, 8-10, and 12-14G. Overall food consumption (days 6-21G) was significantly lower at 100 and 400 mg/kg/day and was reduced 9% and 29% when compared with control group values, respectively. At 50 mg/kg/day, there was a slight, statistically significant reduction in mean food consumption over the first few days o f dosing (days 6-8, 8-10G). These reductions were consistent with the reductions in weight and weight change in that there were minimal, transient, and had no impact on either overall food consumption or final body weight. Thus, these changes were not considered adverse. 5. Clinical Observations (Table 4, Appendix D) Compound-related clinical observations were significantly increased at 400 mg/kg/day and included alopecia, vaginal discharge, salivation after dosing, scab, stained chin fur, and wet and/or stained perineum. At 100 mg/kg/day, salivation after dosing was significantly increased. At 50 mg/kg/day, one rat was observed salivating after dosing. The clinical observations at 400 mg/kg/day were considered adverse with the exception o f the salivation after dosing. The salivation after dosing that was seen in animals at > 50 mg/kg/day was considered the result of taste aversion and/or local irritation rather than evidence o f systemic toxicity. 6. Postmortem Findings (Appendix E) There were no compound-related maternal gross postmortem findings; all animals on study appeared normal at necropsy. B. Fetal Findings 1. Mortality (Table 5, Appendix F) There was no compound-related fetal mortality; data for fetal resorptions and dead fetuses were comparable to controls at all dose levels. - 17- H-24768: Developmental Toxicity Study in Rats DuPont-6515 2. Body Weight (Table 5, Appendices F and G) There was a compound-related, significant reduction in mean fetal body weight at 400 mg/kg/day (13% lower than controls). Mean fetal body weights at 50 and 100 mg/kg/day were generally comparable to controls (within 2% o f control group values). 3. Malformations (Table 6, Appendix G) There were no compound-related fetal malformations at any level tested. There were 3 fetuses from 3 litters (2 at 50 mg/kg/day and one at 100 mg/kg/day) with unrelated non-treatment related malformations and there were no malformed fetuses at 400 mg/kg/day. 4. Variations (Table 7, Appendix G) There were increased compound-related fetal variations at 400 mg/kg/day that were consistent with the reduction in mean fetal body weight (delayed skull bone ossification and supernumerary ribs). There were no increased compound-related fetal variations at 50 or 100 mg/kg/day. - 18- COi'tnpaol tvc*00' TSC* H-24768: Developmental Toxicity Study in Rats DuPont-6515 CONCLUSIONS Under the conditions o f this study, maternal toxicity evident as reduced body weight and food consumption was observed at > 100 mg/kg/day. Non-adverse changes in dams occurred at 50 mg/kg/day and thus, the maternal no-observed-effect level (NOEL)a was considered 50 mg/kg/day. Developmental toxicity was evident at 400 mg/kg/day as reduced fetal weight and increased fetal variations. The NOEL for developmental toxicity was considered 100 mg/kg/day. RECORDS AND SAMPLE STORAGE Laboratory-specific or site-specific raw data, such as personnel files and equipment records will be retained by the facility where the work was done. A sample of the test substance was collected for archive purposes and retained at Haskell Laboratory. Specimens, raw data, and the final report will be retained at Haskell Laboratory, Newark, Delaware, or at Iron Mountain Records Management, Wilmington, Delaware. Clinical pathology slides and raw data will be retained at Haskell Laboratory, Newark, Delaware. Characterization data (percent purity, composition, and known impurities) will be stored at Regional Analytical Services (RAS), Jackson Laboratories, Deepwater, New Jersey. Characterization data used to support test substance stability will be retained at Haskell Laboratory, Newark, Delaware, or at Iron Mountain Records Management, Wilmington, Delaware. a The NOEL for this study is defined as the highest dose at which adverse effects attributable to the test substance were not detected. Thus, for this study, the NOEL is equivalent to the NOEL as defined by the U.S. EPA(12) and to the no-observed-adverse-effect level (NOAEL) as defined by the European Union.(l3) -rso ntfCO*AS.'*' - 19- Sa**' H-24768: Developmental Toxicity Study in Rats DuPont-6515 REFERENCES 1. DuPont Haskell Report Number DuPont-5846, Work Request Numbe Study Service C o ^ J j p y L-- 2. Salewski, E. (1964). Farbemethode zum makroskopischen Nachweis von Implantationstellen am Uterus der Ratte. Archiv. Path. Exp. Pharmakol. 247:367. 3. Staples, R.E. (1974). Detection o f Visceral Alterations in Mammalian Fetuses. Teratology, 9(3):A37-A38. 4. Woo, D.C. and Hoar, R.M. (1972). Apparent Hydronephrosis as a Normal Aspect o f Renal Development in Late Gestation o f Rats: The Effect o f Methyl Salicylate. Teratology, 6:191-196. 5. Barrow, M.V. and Taylor, W.J. (1969). A Rapid Method for Detecting Malformations in Rat Fetuses. J. Morph., 127(3):291-306. 6. Selwyn, M.R. (1995). The Use o f Trend Tests to Determine a No-Observable-Effect Level in Animal Safety Studies. Journal o f the American College o f Toxicology 14(2): 158-168. 7. Haseman, J.K. and Hogan, M.D. (1975). Selection o f the Experimental Unit in Teratology Studies. Teratology, 12:165-171. 8. Patefield, W. (1982). Exact Tests for Trends in Ordered Contingency Tables. Applied Statistics 31:32-43. 9. Snedecor, G.W. and Cochran, W.G. (1967). Statistical Methods, 6th ed. The Iowa State University Press, Iowa, pp. 246-248, 349-352. 10. Jonckheere, A.R. (1954). A Distribution-Free K-Sample Test Against Ordered Alternatives. Biometrika 41:133-145. 11. Dempster, A.P., Selwyn, M.R., Patel, C.M., and Roth, A.J. (1984). Statistical and Computational Aspects of Mixed Model Analysis. The Journal o f the Royal Statistical Society, Series C (Applied Statistics), 33(2):203-214. 12. Hazard Evaluation Division, Standard Evaluation Procedure, Toxicity Potential: Guidance for Analysis and Evaluation o f Subchronic and Chronic Exposure Studies. Paynter, O.E. et al. United States Environmental Protection Agency, Office o f Pesticide Programs, Washington, D.C., 20460. EPA-540/9-85-020, June 1985. 13. Risk Assessment o f Notified New Substances Technical Guidance Document (XI/283/94-EN), Chapter I, Sections 2.24 and 2.25. -20- pompM .jSa'' H-24768: Developmental Toxicity Study in Rats DuPont-6515 TABLES *0^ ,0^ C*V ) H-24768; Developmental Toxicity Study in Rats ) ) DuPont-6515 TABLE 1 MEAN MATERNAL BODY WEIGHTS (grams) ________________________________ DAYS OF G E S T A T I O N ________________________________ GROUP DOSE 0 4 6 7 8 9 ________ mg /kg /day______________________________ ______________ ___________________________________ 10 I0 I I 50 I I I 100 241.5 6.95 22 241.8 6.96 22 242.1 8.65 22 259.7 7.72 22 263.7 11.15 22 258.3 16.29 22 270.3 11.02 22 274.9 10.54 22 268.3 19.94 22 275.6 11.14 22 273.6 11.73 22 262.8* 15.00 22 279.0 10.08 22 274.2 11.70 22 263.5* 12.61 22 286.4 8.69 22 279.0* 12.43 22 268.2* 11.01 22 293.2 8.04 22 286.0* 12.79 22 273.6* 10.69 22 iva 400 242.9 6.73 21 261.5 9.98 21 271.8 8.91 21 255.9* 10.63 21 250.0* 10.68 21 251.1* 11.76 21 254.8* 13.72 21 I H-24768: Developmental Toxicity Study in Rats I DuPont-6515 TABLE 1 (Continued) MEAN MATERNAL BODY WEIGHTS (grams) GROUP DOSE mg/kg/day I0 II 50 III 100 iva 400 11 301.0 9.33 22 294.0 14.12 22 281.6* 10.83 22 260.5* 13.35 21 12 307.0 10.10 22 299.6 14.33 22 288.7* 11.83 22 265.8* 14.41 21 DAYS OF GESTATION 13 14 15 312.3 10.37 22 306.4 14.42 22 294.5* 13.00 22 269.6* 13.16 21 319.0 12.00 22 311.2 14.64 22 298.0* 13.51 22 272.9* 13.37 21 323.1 13.34 22 318.7 16.15 22 304.1* 17.46 22 278.1* 12.82 21 16 333.5 17.37 22 329.8 18.11 22 314.9* 21.34 22 282.2* 14.15 21 17 349.4 14.68 22 344.8 18.78 22 328.1* 25.56 22 293.2* 15.52 21 -23 - H-24768: Developmental Toxicity Study in Rats DuPont-6515 TABLE 1 (Continued) MEAN MATERNAL BODY WEIGHTS (grams) GROUP DOSE mg/kg/day 18 DAYS OF GESTATION 19 20 21 21-b I0 II 50 III 100 366.0 14.48 22 361.6 21.37 22 344.7* 23.87 22 382.1 17.57 22 377.9 23.51 22 361.5* 24.68 22 398.5 16.91 22 394.1 23.09 22 379.6* 27.11 22 423.4 21.36 22 419.4 25.65 22 401.6* 31.01 22 326.8 17.52 22 323.7 14.79 22 308.1* 23.87 22 IVa 400 308.6* 16.56 21 324.2* 16.77 21 338.9* 17.77 21 356.9* 15.98 21 273.1* 13.54 21 Data arranged: M e a n Body Weig h t s (grams) Standard Deviation Number in Group Data from one female that was pregnant by stain were excluded. Body weight calculated using the final body weight minus the weight of the products of conception. Significant trend (linear contrast of means); p < 0.05. -24- 1 H-24768: Developmental Toxicity Study in Rats I TABLE 2 MEAN MATERNAL BODY WEIGHT CHANGES (grams) GROUP DOSE rag/kg/day I0 II 50 III 100 iva 400 4-6 10.6 8.24 22 11.1 4.19 22 10.0 6.64 22 10.3 6.04 21 6-8 8.7 5.29 22 -0.7* 5.93 22 -4.9* 11.24 22 -21.8* 9.67 21 DAYS OF GESTATION 8-10 10-12 12-14 14.2 6.55 22 11.8 3.97 22 10.2* 6.93 22 4.8* 7.26 21 13.9 5.63 22 13.6 4.17 22 15.0 6.51 22 11.0 6.73 21 12.0 5.63 22 11.6 3.75 22 9.4 8.07 22 7.1* 7.67 21 14-16 14.5 13.66 22 18.6 5.39 22 16.8 10.64 22 9.3 6.87 21 16-18 32.6 11.22 22 31.8 5.89 22 29.8 4.76 22 26.4* 8.23 21 I DuPont-6515 ooCX ^ T -25 - ) H-24768: Developmental Toxicity Study in Rats DuPont-6515 TABLE 2 (Continued) MEAN MATERNAL BODY WEIGHT CHANGES (grams) GROUP DOSE mg/kg/day 18-20 DAYS OF GESTATION 20-21 6-21 6-21-k I0 32.5 7.93 22 24.8 7.67 22 153.1 20.29 22 56.5 14.52 22 II 50 III 100 32.5 5.35 22 34.9 7.85 22 25.3 5.74 22 22.0 6.95 22 144.5 21.41 22 133.3* 19.81 22 48.8* 10.53 22 39.8* 16.20 22 IVa 400 30.3 8.25 21 18.0* 5.88 21 85.2* 19.66 21 1.3* 13.21 21 Data arranged: Mean Body Weights (grams) Standard Deviation Number in Group a Data from one female that was pregnant by stain were excluded. b Body weight calculated using the final body weight minus the weight of the products of conception. * Significant trend (linear contrast of means); p < 0.05. meiuoaVu -26- r H-24768: Developmental Toxicity Study in Rats TABLE 3 MEAN MATERNAL FOOD CONSUMPTION (grams/day) GROUP DOSE mg/kg/day I0 II 50 III 100 O 3 T3 I to 3 $Q- ao IVa 400 4-6 22.1 4.71 22 23.8 2.34 22 22.9 5.39 22 24.1 3.26 21 6-8 23.2 2.96 22 20.1* 3.21 22 18.2* 3.56 22 10.1* 4.25 20-b DAYS OF GESTATION 8-10 10-12 12-14 23.9 1.96 22 21.5* 3.40 22 20.6* 3.56 22 13.8* 3.79 2Qb 25.2 2.40 22 24.6 3.09 22 23.4 3.33 22 17.1* 3.54 21 26.9 2.25 22 26.5 2.83 22 24.7* 3.10 22 18.6* 2.56 21 14-16 27.5 6.44 22 27.7 3.51 22 25.6 6.60 22 19.6* 3.80 21 16-18 30.1 3.58 22 30.2 3.19 22 27.9 4.78 22 23.5* 4.24 21 DuPont-6515 nolconta'1 3 to o > H-24768: Developmental Toxicity Study in Rats I ') DuPont-6515 TABLE 3 (Continued) MEAN MATERNAL FOOD CONSUMPTION (grams/day) O 0 1 1 <0 5 N a- a o GROUP DOSE mg/kg/day DAYS OF GESTATION 18-20 20-21 6-21 I0 28.8 2.86 22 27.2 3.95 22 26.5 1.96 22 II 50 28.7 2.78 22 26.1 4.27 22 25.6 2.64 22 III 100 28.2 3.77 22 25.9 4.46 22 24.2* 2.43 22 iva 400 26.3* 3.76 21 23.5* 4.03 21 18.7* 2.17 21 Data arranged: Mean Food Consumption (grams/day) Standard Deviation Number in Group a Data from one female that was pregnant by stain were excluded. b Food consumption data were inadvertently not recorded for female Animal No. 648597 on D a y 8G. * Significant trend (linear contrast of means); p < 0.05. no contain -StO -28- 7) > H-24768: Developmental Toxicity Study in Rats DAY OF GESTATION 4- 5 6-21 TABLE 4 CLINICAL OBSERVATIONS OBSERVATION: GROUP ; DOSE (mg/kg/day) : NO. EXAMINED : NO SIGNS OBSERVED ALOPECIA DIARRHEA DISCHARGE PERINASAL DISCHARGE VAGINAL OPENING SALIVATION SCAB STAIN CAGEBOARD STAIN CHIN STAIN PERINASAL STAIN PERINEUM WET CHIN WET NOSE WET PERINEUM I 0 22 3 0 0 0 0 0 0 0 0 0 0 0 0 II 50 22 6 0 0 0 1 0 1 0 0 0 0 0 0 > * Significant trend (Cochran-Armitage test); p < 0.05. III IV 100 400 22 22 6 14* 01 01 1 3* 5* 14* 1 3* 01 1 3* 01 1 5* 01 01 0 3* DuPont-6515 , jfaiedittOCfe -29- H-24768: Developmental Toxicity Study in Rats DuPont-6515 TABLE 5 REPRODUCTIVE OUTCOME Group: Dose (mg/kg/day): I 0 II III IV 50 100 400 No. Mated No. Pregnant NO Aborted No. Deaths No. With Total Resorptions No. Litters No. Live Fetuses No. Dead Fetuses No. Fetal Resorptions 22 22 0 0 0 22 306 0 9 22 22 0 0 0 22 304 0 4 22 22 0 0 0 22 294 0 15 22 22 0 0 0 21a 286 0 14 Means Per Litter Mean Corpora Luteal Implantations 15.9 (2.23)c 14.3(1.49) 15.1(2.51) 14.0(2.29) 15.7(2.69) 14.0 (2.15) 16.4(3.04) 14.3(1.59) Resorptions : Total Early Late 0.4(1.10) 0.4(1.09) 0.5(0.21) 0.2(0.39) 0.2(0.39) 0.0 0.7(1.73) 0.3 (0.55) 0.4(1.71) 0.7(1.20) 0.6(0.98) 0.1(0.30) Dead Fetuses 0.0 0.0 0.0 0.0 Live Fetuses^: Total Males Females 13.9(1.69) 6.7(2.06) 7.2(2.00) 13.8 (2.20) 7.4 (2.57) 6.5(1.65) 13.4 (2.52) 7.5 (2.70) 5.9 (2.22) 13.6(1.66) 7.0(1.47) 6.6(2.16) Mean Fetal Weight: Total Males Females 5. 5 0 (0.28) 5.64 (0.35) 5.38(0.27) 5.49(0.26) 5.64(0.29) 5.34(0.28) 5.40 (0.39) 5.56(0.34) 5.23 (0.43) 4.76(0.29)* 4.87(0.30) 4.65(0.29) Sex Ratioe 0.48(0.14) 0.52(0.13) 0.55 (0.18) 0.53(0.13) a One animal pregnant by stain. b Statistical analyses are not conducted on mean corpora lutea data; these data are presented for information only. c Standard deviation is reported in parentheses. d Statistical analyses are only conducted on the mean total number of live fetuses per litter. The mean number of males and females are presented for information only. e Number male fetuses/total number fetuses per litter. * Significant trend; p < 0.05. Note: The pregnancy rate data, adult mortality data, and the total resorption data were statistically analyzed using the Cochran-Armitage test. All litter mean data (except for fetal weight and sex ratio) were analyzed using Jonckheere's test. Fetal weight and sex ratio were analyzed using a linear contrast of least square means. -30- not contain TSCA CB ftmparX Sanitized. Does H-24768: Developmental Toxicity Study in Rats DuPont-6515 TABLE 6 INCIDENCE OF FETAL MALFORMATIONS Group: Dose (mg/kg/day): I 0 II III 50 100 EXTERNAL N o . Examined3 Anus - Imperforate Tail - Filamentous No. Affected 306 [22] --- 0 [0] 304 [22] 1 (1) 1(1) 1 [1] 294 [22] ----0 [0] IV 400 286 [21] ----0 [0] VISCERAL N o . Examined Heart &/or Greater Vessels Double Outlet Septal Defect No. Affected 157 [22] 157 [22] 152 [22] ... --- 0 to] --0[0] 1(1) 1 (1) 1[1] 148 [21] --- 0 [0] HEAD N o . Examined Nares - Naris Atresia No. Affected 157 [22] --- 0[0] 157 [22] 1(1) l[l] 152 [22] --- 0 [0] 148 [21] --0 [0] not contain TSCAcm Company Sanitized. Does H-24768: Developmental Toxicity Study in Rats DuPont-6515 TABLE 6 (Continued) INCIDENCE OF FETAL MALFORMATIONS a Group: Dose (mg/kg/day): I 0 II III 50 100 IV 400 SKELETALcN o . Examined No. Affected 303 [22] 0 [0] 2 8 7 [21] 0 0] 293 [22] 0 [0] 2 7 8 [21] 0 [0] TOTAL NUMBER AFFECTED 0 (0) 2 (2) Kl) 0 (0) a Number examined and affected, including the number affected with the listed malformations are expressed as Fetuses[Litters] or Fetuses (Litters) . b For ease of reading, zeros have been replaced with dashes for the listed malformations. c Due to technical errors that occurred during the skeletal processing step, the following skeletal specimens were disarticulated and thus, were unavailable for examination: Group I D a m No. 6 4 8 5 5 3 F e t u s e s No. 5, 6, a n d 11 G r o u p II D am No. 648537 Fetuses 1-17 Group III Dam No. 648599 Fetus 8 Group IV Dam No. 648539 Fetuses 6-9 and 11-14 d Some fetuses were damaged during evisceration, A list of affected fetuses and c o r r e s p o n d i n g b o n e s is p r e s e n t e d in A p p e n d i x G. No significant trends were detected. Note: Statistical analyses are only conducted on the individual endpoints. The overall total and totals by exam type are presented for information only. -32- Ooasf10*cuntoin c g ^ s " ,'BieA H-24768: Developmental Toxicity Study in Rats DuPont-6515 TABLE 7 INCIDENCE OF FETAL VARIATIONS Group: Dose (mg/kg/day): I 0 ii 50 DEVELOPMENTAL VARIATIONS hi 100 IV 400 EXTERNAL N o . Examined3 No. Affected VISCERAL No. Examined No. Affected HEAD N o . Examined No. A f f ected SKELETAL N o . Examined Rib - Supernumerary Sternebra - Misaligned No. Affected 306 [22] --- b 304 [22] 0 [0] 294 [22] 0 [0] 2 8 6 [21] 0 [0] 157 [22] 0 [0] 157 [22] 0 [0] 152[22] 0 [0] 148 [21] 0 to] 157 [22] 0 [0] 157 [22] 0 [0] 152 [22] 0[0] 148 [21] 0 [0] 303 [22] 10 (6) 2 (2) 13 [9] 2 8 7 [21] 11 (6) --11 [S] 293 [22] 21(10) 1 (1) 22[11] 2 7 8 [21] 31(12)* 4 (3) 34[12] TOTAL WITH DEVELOPMENTAL VARIATIONS 13 (9) 11 (6) 22(11) 34(12) -33- . . ^ lSCAC1 Q 0es SanUked. Upupas H-24768: Developmental Toxicity Study in Rats DuPont-6515 TABLE 7 (Continued) INCIDENCE OF FETAL VARIATIONS Group: Dose (mg/kg/day): I 0 II 50 VARIATIONS DUE TO RETARDED DEVELOPMENT EXTERNAL N o . Examined No. A f f e c t e d 3 0 6 [22] 0 [0] 304 [22] 0 [0] III 100 294 [22] 0 [0] IV 400 2 8 6 [21] 0 [0] VISCERAL N o . Examined Kidney, Papillae0 Small Papilla - Size 1 Small Papilla - Size 2 Papilla - Size 3 No. A f f e c t e d HEAD N o . Examined No. A f f e c t e d SKELETAL^ N o . Examined Mandible - Retarded Ossification Rib - Wavy Skull - Retarded Ossification Sternebra - Retarded Ossification Vertebra - Retarded Ossification No. A f f e c t e d 157 [22] 20 (13) --8 (6) 12(11) 20 [13] 157 [22] 30 (16) 2 (2) 12(12) 16(11) 30 [16] 152[22] 31(16) 2 (2) 14 (8) 15(12) 30 [16] 1 4 8 [21] 16 (10) --9 (5) 7 (6) 15 [10] 1 5 7 [22] 0 [0] 1 5 7 [22] 0 [0] 152[22] 0 [0] 148 [21] 0 [0] 303 [22] 4 (1) --- 25 (10) 1(1) 46 (16) 64 [19] 2 8 7 [21] ----- 15(9) 1 (1) 49(16) 59[17] 293 [22] ----- 21(12) --- 38(15) 55[17] 2 7 8 [21] --1 (1) 43 (16)* 7 (3) 49 (16) 88 [20] contain TSC^CBi noi -34- jpompany S .n # l 4 -DuM H-24768: Developmental Toxicity Study in Rats DuPont-6515 TABLE 7 (Continued) INCIDENCE OF FETAL VARIATIONS Group: Dose (mg/kg/day): I 0 II 50 TOTAL WITH VARIATIONS DUE TO RETARDED DEVELOPMENT 83 (21) 84 (20) III 100 82 (22) IV 400 1 0 1 (20) TOTAL NUMBER FETUSES WITH VARIATIONS 94(21) 94(20) 96 (22) 13 0 (21) Number examined and affected, including the number affected with the listed variations, are expressed as Fetuses[Litters] or Fetuses (Litters). For ease of reading, zeros have been replaced with dashes for the listed variations. Statistical analyses are conducted on the combined incidences of small renal papillae; the details for each size are presented for information only. Due to technical errors that occurred during the skeletal processing step, the following skeletal specimens were disarticulated and thus, were unavailable for examination: Group I D a m No. 6 4 8 5 5 3 F e t u s e s No. 5, 6, a n d 11 G r o u p II D a m No. 648537 Fetuses 1-17 Group III Dam No. 648599 Fetus 8 Group IV Da m No. 648539 Fetuses 6-9 and11-14 * Significant trend (Jonckheere's test); p < 0.05. Note: Statistical analyses are only conducted on the individual endpoints. overall total and totals by exam are presented for information only. The Does not contain TSCACB p p pipany Saniti^edi P -35- H-24768: Developmental Toxicity Study in Rats DuPont-6515 APPENDICES not contain t sc a -36- g n a w ppe` pom Pan^ H-24768: Developmental Toxicity Study in Rats DuPont-6515 APPENDIX A Individual Body Weights - 3 7 - PP) ts c * noic*>w H-24768: Developmental Toxicity Study in Rats Individual Body Weights Explanatory Notes Footnotes a Maternal body weight minus the weight of the products of conception. b Pregnant by stain. Data excluded from the calculations. Abbreviations -----= No Data DuPont-6515 TSCADBt S an itized . Does n0t contain jpompani -38- H-24768: Developmental Toxicity Study in Rats DuPont-6515 G R O U P I: 0 M G / K G / D A Y ANIMAL NUMBER DAY 0 648517 648520 648522 648528 648535 648536 648544 648549 648553 648554 648559 648566 648567 648571 648573 648576 648582 648587 648588 648592 648601 648602 243.0 257.0 245.0 238.0 230.0 237.0 250.0 237.0 248.0 246.0 245.0 232.0 243.0 245.0 235.0 241.0 241.0 241.0 238.0 234.0 234.0 254.0 INDIVIDUAL B O D Y W E I G H T S (grams) DAY 4 256.7 252.4 262.0 250.7 241.8 253.0 257.3 255.8 266.6 267.4 265.7 256.5 259.6 266.7 262.8 247.8 261.9 261.5 263.3 268.2 260.1 276.1 DAYS OF GESTATION DAY 6 DAY 7 DAY 8 276.8 232.0 278.0 273.3 257.2 268.9 267.6 265.9 273.1 279.7 275.7 266.7 264.3 275.9 269.9 260.2 269.6 271.6 274.1 280.0 278.8 287.1 278.3 238.0 290.4 284.0 263.6 278.6 280.4 268.4 273.0 281.3 275.0 278.9 269.2 285.2 274.3 264.5 275.1 274.7 276.5 281.7 279.0 293.1 287.3 253.0 296.1 279.8 258.3 274.6 283.8 274.2 274.8 289.5 283.7 278.8 271.4 281.1 283.7 271.3 280.5 276.1 278.1 286.9 279.9 294.3 DAY 9 D A Y 10 298.7 274.5 303.0 285.7 268.1 283.0 289.6 282.8 284.0 294.7 289.9 285.3 275.8 284.5 282.7 274.1 287.5 284.0 286.7 295.4 290.6 299.5 300.8 291.5 314.7 297.1 276.2 289.7 288.7 286.0 291.0 301.7 294.3 289.6 284.1 296.3 289.3 283.5 292.7 294.1 293.2 295.7 294.5 305.2 -39- pmpart s m l w > eS H-24768: Developmental Toxicity Study in Rats DuPont-6515 GROUP I: 0 MG/KG/DAY ANIMAL NUMBER DAY 11 INDIVIDUAL BODY WEIGHTS (grams) DAY 12 DAYS OF GESTATION DAY 13 DAY 14 DAY 15 DAY 16 DAY 17 648517 648520 648522 648528 648535 648536 648544 648549 648553 648554 648559 648566 648567 648571 648573 648576 648582 648587 648588 648592 648601 648602 306.,3 302.,8 312..7 2 9 5 ..1 276 ..4 294 ..8 309 .9 299..2 304 .,1 322 .2 3 0 1 .1 296 .0 2 9 0 .8 3 0 6 .2 2 9 6 .0 2 9 2 .0 300 .7 2 9 8 .0 298 .9 303 .3 302 .1 313 .5 312 .,2 315.,8 329..5 302.,5 2 8 4 ..0 3 0 6 ..7 3 1 6 ,.1 300..0 3 0 9 .7 318 ,.4 3 0 9 ,.5 304 .0 293 .1 305 .0 301..1 294 .9 309..0 2 9 9 .8 2 9 9 .8 314 .7 310 .2 319 .0 325 .,2 314 .,6 336.,1 310.,3 294 .,0 310.,2 322 ..9 307,.6 313 .3 318,.8 312 .7 302 .4 301 .4 302 .0 305 .0 298 .2 312 .3 310 .1 305 .1 320 .5 321 .4 327 .1 321..8 3 2 4 ..2 3 4 5 ..7 319..5 2 9 5 ..1 3 1 3 ..8 3 2 3 ..6 3 0 2 .2 3 1 6 .7 3 2 8 .3 3 1 8 .3 3 1 2 .1 306..8 3 1 2 .3 3 1 3 .3 3 0 8 .5 321..3 315 .9 321..4 325 .6 3 2 4 .6 3 4 7 .3 3 2 5 .5 291..0 346..1 319..5 296..0 317 .0 334 .1 312 .8 323 .3 339..2 327 .5 318 .8 317 .2 321..7 322 .4 314 .2 332 .6 320 .4 318 .9 335 .7 332 .0 343 .0 336..9 283 ..7 3 5 7 ,.6 341..9 303 .7 326 .4 345 .3 325 .4 337,.0 352 .9 3 3 6 ,.0 3 1 9 ,.0 329,.6 330..1 329,.3 321,.5 3 3 2 ,.1 336,.1 331,.0 351,.8 3 5 1 .2 3 5 7 .8 3 5 1 .0 3 3 8 .5 3 6 6 .4 3 5 4 .6 3 1 4 .1 3 3 8 .1 36 2 .1 333 .8 351,.1 3 7 2 ,.1 3 4 8 .4 3 3 1 .0 346..9 3 4 2 .2 350..2 338..7 343 .9 353 .3 3 4 2 .4 367..0 3 6 8 .4 3 7 2 .1 Sam1 pmPgff -(SC^cB' to' conva'm -40- H-24768: Developmental Toxicity Study in Rats GROUP I: 0 MG/KG/DAY ANIMAL NUMBER DAY 18 INDIVIDUAL BODY WEIGHTS (grams) DAYS OF GESTATION DAY 19 DAY 20 DAY 21 DAY 21a 648517 648520 648522 648528 648535 648536 648544 648549 648553 648554 648559 648566 648567 648571 648573 648576 648582 648587 64B588 648592 648601 648602 358..7 358..9 382 .7 368,.1 3 3 3 ,.1 345..5 385..2 354 ,.1 374 ,.6 390 .7 368..7 356..4 366 .2 366 ,.0 363 .7 352 .2 3 6 5 ,.9 365 .6 3 5 0 .7 3 7 7 ..7 381,.0 386 .7 381 .2 381..8 409..8 392,.4 350..4 365..9 401..4 372..1 390..2 412,.3 3 9 0 ,.8 359 .2 377 .0 374 ,.0 374 ,.8 360 .1 374 .4 3 7 9 .0 358 .8 397,.2 398 .0 406 .0 393..2 410.,6 414 ,5 404,.0 372,.4 381..5 411..8 381.,2 407..3 428..6 404 ,.1 378 ,.7 391 .4 385,.8 386..5 374 .2 392 .1 399 .7 386,.7 418 .2 425..1 420 .2 4 0 6 .7 433 ,.1 442 .3 4 3 7 .1 394 .8 393 .9 4 4 0 .4 3 9 8 .6 436 .7 4 7 1 .6 430,.0 404 .4 422 .5 413 .4 4 1 9 .9 396 .7 4 1 9 .1 4 1 1 .6 401..3 4 4 0 .1 4 4 9 .5 450 .5 326 ,.5 319..0 355..9 336..0 293 .7 307 .9 342 .,2 307 .,4 336 ,2 3 4 8 ,.7 331..4 303 ,.0 3 1 9 .6 325 ,.7 3 2 7 ,.9 306 ,.3 332 ,.5 3 0 6 ,.7 321..8 345 ..0 352 .,0 344 .8 DuPont-6515 -41 - n0, c ^ TSfcCB' Ooe popany Santf*ed H-24768: Developmental Toxicity Study in Rats G R O U P II: 50 M G / K G / D A Y ANIMAL NUMBER DAY 0 INDIVIDUAL BODY WEIGHTS (grams) DAY 4 DAYS OF GESTATION DAY 6 DAY 7 DAY 8 548518 548524 548529 648531 648537 648538 648541 648542 648546 648547 648551 648562 648564 648565 648574 648575 648580 648585 648591 648596 648598 648600 247.0 240.0 257.0 233.0 248.0 232.0 247.0 246.0 250.0 243.0 240.0 233.0 249.0 245.0 244.0 236.0 234.0 240.0 239.0 237.0 231.0 248.0 262.9 268.1 281.3 249.8 267.9 248.5 269.3 272.8 283.9 274.6 244.6 255.0 278.7 260.7 268.7 262.7 260.3 263.9 257.2 262.3 242.8 266.4 279.2 283.0 299.7 264.5 278.5 267.3 278.0 282.3 293.6 279.0 259.5 264.5 285.3 268.3 276.4 265.2 270.7 277.3 269.2 272.5 255.9 277.8 279.0 285.6 296.5 262.5 276.7 257.7 272.9 287.7 292.6 273.9 255.4 258.5 289.3 268.3 281.1 269.9 265.9 274.5 268.9 271.7 257.6 272.8 271.8 280.7 297.4 260.0 283.5 262.8 266.8 288.5 289.9 284.0 257.2 258.2 288.0 266.9 286.9 272.8 274.9 278.4 269.1 2 6 B .2 261.0 266.4 DuPont-6515 DAY 9 D A Y 10 277.0 287.6 296.9 266.1 286.6 265.7 273.2 297.0 296.6 288.2 262.6 262.6 291.6 269.5 297.8 272.9 284.5 284.3 277.5 265.4 266.8 268.0 282.0 295.8 307.7 275.5 292.5 272.0 277.5 305.2 299.7 291.3 264.2 277.9 306.0 279.6 303.7 277.6 290.5 289.0 282.3 277.3 269.9 275.8 TSCAC ---4--2----------p--o-m---p--annvy uaim*odi no<?s n l C nta H-24768: Developmental Toxicity Study in Rats DuPont-6515 INDIVIDUAL BODY WEIGHTS (grams) GROUP II: 50 MG/KG/DAY ANIMAL NUMBER D A Y 11 D A Y 12 DAYS OF GESTATION D A Y 13 D A Y 14 D A Y 15 DAY 16 D A Y 17 648518 648524 648529 648531 648537 648538 648541 648542 648546 648547 648551 648562 648564 648565 648574 648575 648580 648585 648591 648596 648598 648600 286.1 299.4 318.8 278.0 301.1 285.3 286.5 312.2 305.1 308.1 275.4 279.2 316.0 277.9 314.1 288.9 301.3 299.5 292.2 283.2 274.7 285.2 295.3 308.1 320.8 286.3 310.7 287.2 297.3 315.8 312.7 308.7 278.2 283.4 319.4 286.0 323.7 293.5 308.7 307.0 295.3 283.7 280.0 290.2 296.2 324.4 321.6 293.0 318.8 297.1 303.6 322.0 324.0 317.4 285.0 293.6 326.1 288.4 326.3 300.4 309.1 315.2 301.0 290.2 285.6 300.9 300.8 327.5 332.9 295.7 322.1 302.8 304.1 328.5 318.2 322.5 292.5 297.1 329.7 291.7 334.2 300.0 320.0 322.0 309.4 299.0 292.0 303.5 303.2 339.0 336.5 298.4 327.2 307.4 311.3 341.0 331.3 328.5 299.5 302.2 343.5 299.5 343.1 309.3 325.5 331.7 314.5 307.0 300.2 310.5 308.2 355.0 353.4 305.7 339.5 318.1 319.0 351.2 339.0 343.3 312.8 306.9 356.0 310.5 351.4 322.7 335.8 350.2 329.8 315.2 307.9 323.3 324.7 360.9 369.5 319.6 356.4 326.7 330.9 368.4 352.8 355.2 327.1 325.8 375.5 328.1 377.1 337.4 353.6 363.3 343.8 332.5 325.1 332.3 -- --------- ^ .i-.-f -D---o-0--s--n--o-'-c--o-"--,-a-"--'-1--S--C'' H-24768: Developmental Toxicity Study in Rats INDIVIDUAL BODY WEIGHTS (grams) GROUP II: 50 MG/KG/DAY ANIMAL NUMBER DAY 18 DAYS OF GESTATION DAY 19 DAY 20 DAY 21 DAY 21a 648518 648524 648529 648531 648537 648538 648541 648542 648546 648547 648551 648562 648564 648565 648574 648575 648580 648585 648591 648596 648598 648600 331 .2 386 .3 386 .3 328 .6 371 .6 3 4 1 .8 353 .0 393 .2 365 .0 377 .7 3 4 6 .1 343 .8 394 .8 343 .2 387.,4 3 5 9 .2 375 .5 385 .0 3 5 0 ..7 3 4 8 ..9 335..1 3 5 0 ..3 346 .2 410 .2 392 .7 343 .2 390..8 368,.0 373 .7 412 .0 383,.8 397..6 362 .8 349,.5 415..6 358..8 4 0 6 .6 372..2 3 8 1 .8 4 0 8 ,.9 366,.2 367,,7 344 ,.7 361..4 365..6 419..9 413 ,.9 359..3 407,.0 384..4 383 .9 428,.9 390,.9 415..7 377..5 366 .7 428..5 367..5 425..4 390..3 400..5 427,.0 386 .8 382 .2 369..5 379 .0 390..0 453 .9 440 .8 378 .9 438..2 414 .6 396 .2 451..1 412..0 454 ,.2 400 .0 395 .9 454 ,.9 389..5 4 5 0 .0 410 .3 430 .9 450 .6 407 .8 410 .3 389 .6 406 .5 317 .9 325 .0 341 .9 312 .4 326 .1 313 .1. 306 .9 337 .5 335 .8 343 .3 306 .9 315 .7 336 .,9 312 .3 345 .4 308 .7 341 .6 342 .6 318 .6 319 .3 293 .9 319 .6 DuPont-6515 not contain tSCACo* -44- H-24768: Developmental Toxicity Study in Rats DuPont-6515 INDIVIDUAL BO D Y WEIGHTS (grams) G R O U P III: 100 M G / K G / D A Y ANIMAL NUMBER DAY 0 DAY 4 DAYS OF GESTATION DAY 6 DAY 7 DAY 8 648519 648521 648527 648530 648533 648543 648545 648548 648550 648557 648558 648568 648569 648572 648578 648581 648593 648594 648595 648599 648603 648604 249.0 233.0 242.0 237.0 240.0 264.0 244.0 248.0 257.0 231.0 236.0 251.0 231.0 239.0 245.0 243.0 248.0 246.0 241.0 234.0 237.0 230.0 265.4 258.5 264.7 262.4 252.1 286.2 261.4 263.3 274.5 254.7 216.7 272.8 260.7 261.1 250.3 264.3 265.1 270.7 227.6 264.3 261.5 225.2 283.2 276.8 278.6 274.4 268.8 298.8 266.4 275.0 282.5 265.9 204.7 283.0 268.4 268.0 270.3 272.2 269.1 282.3 239.6 269.6 274.3 231.1 273.5 271.2 259.1 266.7 264.3 288.3 260.6 262.0 276.9 254.8 219.0 273.7 262.2 269.4 264.2 257.2 265.6 270.7 247.1 269.1 274.1 231.3 275.9 274.0 255.3 253.4 261.6 276.8 256.5 263.4 281.9 255.1 234.3 273.4 262.3 269.1 265.7 269.9 265.2 276.3 251.3 267.8 272.2 234.7 DAY 9 D A Y 10 276.9 273.5 269.6 254.0 272.7 273.1 267.1 279.1 271.8 264.1 244.1 282.5 267.3 269.1 270.9 273.7 265.9 285.3 252.4 266.3 276.4 243.7 283.7 284.6 278.7 271.4 278.6 268.5 265.3 274.2 283.2 266.4 249.1 282.2 272.4 278.5 280.0 274.4 277.1 290.9 268.1 266.0 279.7 247.1 -45 - poe8 nQ\conla'in pmPan* ? an'Uzed H-24768: Developmental Toxicity Study in Rats DuPont-6515 INDIVIDUAL BODY WEIGHTS (grams) GROUP III: 100 MG/KG/DAY ANIMAL NUMBER D A Y 11 D A Y 12 DAYS OF GESTATION D A Y 13 DAY 14 DAY 15 DAY 16 DAY 17 648519 648521 648527 648530 648533 648543 648545 648548 648550 648557 648558 648568 648569 648572 648578 648581 648593 648594 648595 648599 648603 648604 287.7 290.5 283.0 269.7 284.9 288.2 283.1 282.1 293.7 278.9 265.5 296.4 278.6 285.9 287.6 286.7 283.3 294.9 271.3 271.6 283.3 249.4 300.4 297.8 294.1 267.7 296.2 299.3 282.4 294.3 299.4 283.0 271.2 300.1 288.1 293.2 292.6 296.3 287.9 301.3 278.0 273.2 293.7 260.5 308.5 300.4 302.7 279.7 302.0 306.8 287.1 305.7 312.3 284.7 269.4 300.1 297.1 293.0 295.6 297.6 293.9 314.7 281.9 282.6 296.9 265.6 3 1 0 .9 3 0 9 .1 306 .7 2 8 9 .7 287,.8 306..6 2 8 9 .8 300..8 3 1 1 .9 282 .5 263 .5 304 .9 2 9 7 .1 302 .7 301..8 3 0 0 ..6 3 0 5 ..6 3 2 2 ..2 2 8 5 ..6 2 9 5 ..8 3 0 6 ..6 2 7 4 ..4 3 1 7 .7 3 0 7 .6 3 1 0 .9 2 8 9 .6 277 .8 317 .6 301 .1 314 .2 317 .4 289 .6 255 .4 320 .8 308 .1 306 .9 314 .3 318 .0 3 0 9 .0 3 2 8 .3 2 9 8 ..2 2 9 8 ..5 314 ..1 2 7 5 ..3 333..8 320..5 315 ,.6 300 .7 282..4 328..9 313 .5 326 .1 332 .1 305 .0 247 .9 328 .3 317 .9 316 .3 317 .7 324 ,.8 320,.5 354,.5 312 ,.0 312 ,.9 326..6 289 .,1 348 .8 3 2 8 ..7 327..2 314 .6 2 7 9 .6 3 3 8 ,.0 3 2 6 ..0 343 .2 3 4 8 .4 317 ,.4 2 4 8 .6 347 .6 333 .6 342 ,.8 330 .0 345 .7 339,.7 3 6 6 ,.8 329..0 3 2 2 ..6 340..8 299..5 TSCACb 46- H-24768: Developmental Toxicity Study in Rats INDIVIDUAL BODY WEIGHTS (grams) GROUP III: 100 MG/KG/DAY ANIMAL NUMBER D AY 18 DAYS OF GESTATION DAY 19 DA Y 20 DAY 21 DAY 21 648519 648521 648527 648530 648533 648543 648545 648548 648550 648557 648558 648568 648569 648572 648578 648581 648593 648594 648595 648599 648603 648604 358..7 344 .4 344 ,.3 327..8 309..8 358..8 348 .9 363..6 364 ,.1 332 .9 273 .5 363 .4 345..0 350 .7 3 4 5 .3 359 .9 357 .5 388..9 3 3 6 .6 3 3 5 ,.5 359,.9 313 .2 381..7 366..7 356..6 347..7 336..3 376..9 368 .1 382 .2 385 .9 360 .8 289..4 386 .1 354 .6 357 .1 356..4 378 .1 370 .1 406..7 352 .9 348 .8 369,.5 321..3 399 .6 386 .6 371 .0 365..9 354 .8 389,.8 381..8 398 .5 410..8 372 .0 301..7 404 .4 369..0 372..3 371..5 401..3 392 .7 4 3 8 .2 375 .2 364 ,.7 386 ,.2 343 .1 418 .8 407 .4 393 .0 384 .0 373 .3 404 .9 403 .7 433 .3 4 3 8 .3 386 .9 308 .3 4 3 8 .8 399..2 4 0 0 .1 404 .3 423 .1 4 0 9 .0 459 .3 393 ,.9 385..1 4 1 0 ,.2 3 5 9 ,.9 331 .4 299 .6 322 .2 2 8 9 .9 281 .0 311 .4 304 .2 330 .4 324 .3 293 .7 237..8 344 .2 303 .8 302 .8 3 1 5 ..5 3 2 4 .5 304 .0 3 3 9 .6 3 1 7 .0 301 .6 323 .7 2 7 5 ,.0 DuPont-6515 SCftCB n0i co n tai T -47- H-24768: Developmental Toxicity Study in Rats DuPont-6515 INDIVIDUAL BODY W E I G H T S (grams) G R O U P IV: 400 M G / K G / D A Y ANIMAL NUMBER DAY 0 DAY 4 DAYS OF GESTATION DAY 6 DAY 7 DAY 8 648523 648525 648526 648532 648534 648539 648540 648552 648555 648556 648560 648561* 648563 648570 648577 648579 648583 648584 648586 648589 648590 648597 252.0 236.0 247.0 245.0 233.0 245.0 244.0 254.0 247.0 237.0 250.0 234.0 245.0 240.0 249.0 234.0 241.0 235.0 232.0 246.0 237.0 251.0 258.9 235.5 259.6 254.6 254.0 271.9 257.4 280.3 255.3 261.1 280.0 248.8 271.0 267.2 259.2 249.4 263.2 262.0 258.1 260.8 262.8 268.6 277.0 252.3 271.5 280.4 263.2 280.8 275.3 290.2 269.0 263.9 282.6 253.3 277.4 268.9 265.9 254.8 273.0 274.0 268.9 269.1 277.0 272.0 278.4 244.9 253.7 260.6 244.8 259.2 250.6 271.7 243.1 244.5 264.2 233.3 275.2 258.2 242.8 246.5 267.0 251.6 252.0 251.6 259.8 254.1 267.7 248.5 241.1 248.7 237.7 246.5 234.7 269.5 236.3 242.3 259.1 231.6 267.3 259.5 244.5 242.3 261.4 247.9 246.5 246.1 259.1 242.7 DAY 9 D A Y 10 268.8 252.5 241.2 241.9 240.2 243.5 233.2 261.3 234.9 234.3 267.4 232.0 262.7 262.1 261.9 244.6 264.3 247.9 251.9 248.7 265.4 244.3 274.4 259.7 245.2 234.4 238.3 242.4 231.8 269.4 243.0 242.6 275.3 240.8 268.3 269.3 257.7 253.0 267.0 249.1 257.8 258.1 270.4 243.6 tS C ^ c ' noi - 4 8 - Sawas s * " * H-24768: Developmental Toxicity Study in Rats DuPont-6515 INDIVIDUAL BODY WEIGHTS (grams) GROUP IV: 400 MG/KG/DAY ANIMAL NUMBER D AY 11 D A Y 12 DAYS OF GESTATION D A Y 13 D A Y 14 D A Y 15 D A Y 16 D A Y 17 648523 648525 648526 648532 648534 648539 648540 648552 648555 648556 648560 648561 648563 648570 648577 648579 648583 648584 648586 648589 648590 648597 272.0 263.6 252.7 235.3 240.2 253.4 241.8 272.3 246.8 248.7 281.4 240.1 268.8 276.1 254.1 260.2 272.9 259.2 271.0 260.2 280.3 259.6 280.0 264.8 263.1 233.3 254.6 256.4 242.6 273.2 249.5 258.7 285.0 240.8 278.3 282.8 259.7 270.6 278.5 266.3 261.0 265.3 292.3 266.7 284.7 264.9 264.4 243.7 259.3 263.9 251.0 278.4 248.7 268.0 293.0 235.2 282.8 281.7 262.8 272.9 279.4 266.8 260.9 272.4 289.4 273.0 291.0 267.3 272.9 257.7 270.5 260.9 254.0 276.8 247.4 268.4 295.9 235.7 293.8 282.1 269.5 282.5 268.1 268.3 260.1 276.6 293.3 274.3 292.4 269.7 278.2 263.2 281.1 265.0 258.0 292.9 253.4 272.5 296.3 238.9 298.3 283.6 275.1 289.5 270.0 274.5 271.8 283.8 294.8 275.6 298.6 278.0 284.5 259.3 287.0 270.2 251.3 301.3 256.0 276.3 294.7 240.6 296.0 284.2 279.6 293.2 273.8 284.3 281.0 291.4 300.4 285.0 308.7 294.8 292.3 260.5 292.7 279.7 261.9 311.4 267.4 287.1 301.7 250.3 307.3 290.9 305.3 304.6 286.3 294.0 304.7 301.4 315.4 289.0 f D o e s no!containTSCACBI -49- Pumpany H-24768: Developmental Toxicity Study in Rats INDIVIDUAL BODY WEIGHTS (grams) GROUP IV: 400 MG/KG/DAY ANIMAL NUMBER D A Y 18 DAYS OF GESTATION DAY 19 DAY 20 DAY 21 DAY C21 648523 648525 648526 648532 648534 648539 648540 648552 648555 648556 648560 648561 648563 648570 648577 648579 648583 648584 648586 648589 648590 648597 326 .,1 313 ..5 310 ..7 266 ..1 305 ..2 289..2 276 ..8 318 ,.6 285 .6 302 .6 323 ,.1 2 5 0 ,.8 320 .1 303 .2 317 .7 316..4 309 .3 312 .0 325 .9 322 .9 324 .0 311 .9 3 3 8 ..6 334..8 3 3 2 .9 271..8 3 1 4 .3 3 1 1 .4 300 .4 336 .7 306 .6 327..8 337..3 254 .7 333 .3 312 .7 336 .7 335 .2 316 .9 329 .3 341 .6 333 .1 330 .9 326 .6 356,.2 355..3 344 .0 281 .2 338 .6 335 .6 313 .2 347 .0 326 .0 340 .9 351 .1 262 .3 346 .2 317 .7 346 .8 350 .6 327 .6 343 .7 355 .7 350 .7 345 .8 343 .0 383 .3 369..7 3 6 2 ,.3 314 .2 3 5 0 .3 350..3 331..2 3 6 7 ,.0 3 4 8 .4 3 5 5 .2 366..8 271..1 366..3 343 .3 3 7 0 ,.5 370..3 334,.8 357,.1 369..0 3 6 5 .4 361..5 3 5 9 .0 2 8 3 ..9 269.,8 275..1 2 4 0 ..1 2 5 8 ..7 2 7 0 ..0 2 5 4 ..3 298 ..4 268 .3 275 ..0 286..6 -- 294,.8 268..1 280..5 254 ..2 274 ..9 272 ..5 278 ..9 275 ..3 274 ..7 281,.4 DuPont-6515 ,,taWtSCACBl Does notco -50- H-24768: Developmental Toxicity Study in Rats DuPont-6515 APPENDIX B Individual Body Weight Changes -51 - nnP.a not contain T S C A C ^ Polhpany Sanitized H-24768: Developmental Toxicity Study in Rats Individual Body Weight Changes Explanatory Notes Footnotes a Maternal body weight minus the weight o f the products o f conception. b Pregnant by stain. Data excluded from the calculations. Abbreviations -----= No Data DuPont-6515 n,,l contain TSCACBI -52- i^g|wpgnv^w >rtiae^` ^ eS H-24768: Developmental Toxicity Study in Rats GROUP I : 0 MG/KG/DAY ANIMAL NUMBER 4--6 INDIVIDUAL BODY WEIG H T CHANGES (grams) 6--8 DAYS OF GESTATION 8-10 10-12 12-14 14-16 648517 648520 648522 648528 648535 648536 648544 648549 648553 648554 648559 648566 648567 648571 648573 648576 648582 648587 648588 648592 648601 648602 20 .1 -20 .4 16 .0 22 .6 15 .4 15 .9 10 .3 10 .1 6 .5 12 .3 10 .0 10 .2 4 .7 9 .2 7 .1 12 .4 7 .7 10 .1 10 .,8 11,.8 18..7 11..0 10 .5 21 .0 18 .1 6 .5 1 .1 5 .7 16 .2 8 .3 1 .7 9 .8 8 .0 12 .1 7..1 5 .2 13..8 11..1 10..9 4 .5 4 .0 6,.9 1,.1 7..2 13 ,.5 38 ,.5 18,.6 17,.3 17 .9 15..1 4 ..9 11..8 16..2 12 ,.2 10..6 10 .8 12 .7 15 ,.2 5 ,.6 12 .2 12 ..2 18..0 15 ..1 8.,8 14 ..6 10 .9 11,,4 24 ..3 14 .8 5 .4 7 .8 17..0 27 .4 14 ,.0 18 .7 16 .7 15 .2 14 .4 9 ,.0 8 .7 11..8 11,.4 16 ,.3 5 .7 6 .6 19..0 15 .7 13 .8 9..6 8 ..4 16 .2 17..0 11,.1 7 ,.1 7 ,.5 2 .2 7 .0 9 .9 8 .8 8 .1 13 ,.7 7..3 12 .2 13 ,.6 12 .3 16 ,.1 21..6 10 .9 14 .4 28 .3 15 .1 -40..5 11 .9 22 .4 8 .6 12 .6 21 ,7 23 .2 20 .3 24 .6 17 .7 6 .9 22 .8 17 .8 16 .0 13 .0 10 .8 20..2 9 .6 26 .2 26 .6 10 .5 DuPont-6515 16-18 21..8 75 ..2 25 ,.1 26 .2 29..4 19..1 39 ..9 28..7 37..6 37 .8 32 .7 37 ,.4 36 ..6 35 ,.9 34 ..4 30..7 33 ..8 29..5 19 ..7 25..9 29..8 28..9 -53 - ^ed` *oes not contain TSCA CBI H-24768: Developmental Toxicity Study in Rats GROUP I : 0 MG/KG/DAY ANIMAL NUMBER 18-20 INDIVIDUAL BODY WEIGHT CHANGES (grams) 20-21 DAYS OF GESTATION 6-21 6-21a 648517 648520 648522 648528 648535 648536 648544 648549 648553 648554 648559 648566 648567 648571 648573 648576 648582 648587 648588 648592 648601 648602 34 .5 51 .7 31 .8 35 .9 39 .3 36 .0 26 .6 27 .1 32 .7 37 .9 35 .4 22 .3 25 ,2 19 ,.8 22 ,.8 22 ,.0 26 ,.2 34 .1 36 ..0 40 ..5 44 ..1 33 ..5 13 .5 22 .5 27 .8 33 .1 22 .4 12 .4 28,.6 17 .4 29 .4 43 .0 25 .9 25 .7 31..1 27 .6 33 ,.4 22 ,.5 27,.0 11..9 14 .6 21..9 24 ..4 30..3 129 .9 201 .1 164 ,.3 163 .8 137 .6 125 ,.0 172 ,.8 132 ,.7 163 ,.6 191 .9 154 .3 137 .7 158..2 137..5 150,.0 136..5 149..5 140..0 127..2 160..1 170..7 163 ..4 49 .7 87..0 77 .9 62 .7 36 ,.5 39..0 74 .6 41..5 63 ..1 69..0 55 ,.7 36..3 55 .4 49 ,.8 58 .0 46 .1 62 ..9 35 .,1 47 .7 65..0 73 .2 57..7 DuPont-6515 -54- tscacbI n0t contain pompaPy Sam*d-pneS H-24768: Developmental Toxicity Study in Rats DuPont-6515 INDIVIDUAL BODY WEIGHT CHANGES (grams) G R O U P II: 50 M G / K G / D A Y ANIMAL NUMBER 4--6 6--8 DAYS OF GESTATION 8-10 10-12 12-14 14-16 648518 648524 648529 648531 648537 648538 648541 648542 648546 648547 648551 648562 648564 648565 648574 648575 648580 648585 648591 648596 648598 648600 16 .3 14 .9 18 .4 14 .7 10 .6 18 .8 8 .7 9 .5 9 ,7 4 .4 14 .9 9 .5 6 .6 7 .6 7 .7 2 ,.5 10 ,.4 13 ,.4 12 .,0 10 ,.2 13 ,.1 11 ,.4 -7 .4 -2 .3 -2 .3 -4 .5 5 .0 -4 .5 -11 .2 6 .2 -3 .7 5 .0 -2 .3 -6 .3 2 .7 -1 .4 10 .5 7 .6 4 .2 1 .1 -0 .1 -4 .3 5 ,.1 -11 .4 10 .2 15 .1 10 .3 15 .5 9 .0 9 .2 10 .7 16 .7 9 .8 7 .3 7 .0 19 .7 18,.0 12 ,.7 16,.8 4 ,.8 15 ,.6 10.,6 13..2 9,,1 8.,9 9..4 13 .3 12 .3 13 .1 10 .8 18 .2 15 .2 19 .8 10 .6 13 .0 17 .4 14 .0 5 .5 13 .4 6 .4 20 ,.0 15 .9 18 .2 18 .0 13 .0 6 ,.4 10..1 14 .4 5..5 19..4 12 .1 9 .4 11 .4 15 .6 6 .8 12 .7 5 .5 13 .8 14 .3 13 ,.7 10 ,.3 5 ,.7 10..5 6 ,.5 11..3 15 .0 14 .1 15 .3 12 .0 13 .3 7,.4 27,.5 20 .5 10,.0 17,.4 15,.3 14 ,.9 22 .7 20,.8 20 .8 20,,3 9,,8 26,.3 18.,8 17..2 22 ,7 15 ,.8 28 ,.2 20 ,.4 16 .2 15 .9 19,.8 16-18 23 .0 31 .3 32 .9 22 .9 32 .1 23 .7 34 .0 42 .0 26 ,.0 34 ,.4 33 ,.3 36 ,.9 38 .8 32 ,.7 36..0 36 .5 39..7 34 .8 20 .9 33 .7 27..2 27 ,.0 PM . n . l t " '" TSCACB1 -55- omp&nXSanitized H-24768: Developmental Toxicity Study in Rats INDIVIDUAL BODY W E I G H T CHANGES (grams) G R O U P II: 50 M G / K G / D A Y ANIMAL NUMBER 18-20 20-21 DAYS OF GESTATION 6-21 6- 21a 648518 648524 648529 648531 648537 648538 648541 648542 648546 648547 648551 648562 648564 648565 648574 648575 648580 648585 648591 648596 648598 648600 34 .4 33 .6 27,.6 30 ,7 35 ,.4 42 ,6 30,.9 35,.7 25 ,.9 38 ,0 31,.4 22 ,9 33 ,.7 24 ,.3 38 .,0 31,.1 25 ,.0 42 ,.0 36 ,.1 33 ,.3 34 ,.4 28 ,.7 24 .4 34 .0 26 ,9 19 .6 31 .2 30 .2 12 .3 22 ,.2 21 .1 38 .5 22 ,.5 29,.2 26,.4 22 ,.0 24 .6 20,.0 30 ,4 23 .6 21,.0 28 ,.1 20 .,1 27 ,.5 110 .8 170 .9 141 .1 114 ,4 159,.7 147..3 118 .2 168 ,.8 118 ,.4 175 ,.2 140 .,5 131..4 169 .,6 121.,2 173 .,6 145,,1 160,.2 173 ..3 138 .,6 137,.8 133 .,7 128..7 38 .7 42 .0 42 .2 47 ,.9 47 ,.6 45 ,.8 28 ,.9 55 ,.2 42 ,2 64 ,.3 47 ,.4 51.,2 51. 6 44 ..0 69. 0 43 ..5 70 ..9 65 .,3 49..4 46 .,8 38 ..0 41..8 DuPont-6515 (tcontainTSCACBl santtftcd. pnes -56- omPan H-24768: Developmental Toxicity Study in Rats INDIVIDUAL BODY WEIGHT CHANGES (grams) GROUP III: 100 MG/KG/DAY ANIMAL NUMBER 4--6 6--8 DAYS OF GESTATION 8-:10 io-:12 12-:14 14- 16 648519 648521 648527 648530 648533 648543 648545 648548 648550 648557 648558 648568 648569 648572 648578 648581 648593 648594 648595 648599 648603 648604 17..8 18..3 13..9 12 ..0 16..7 12..6 5 ..0 11,.7 8..0 11..2 -12 .0 10 .2 7..7 6 .9 20..0 7,.9 4 .0 11,.6 12 .0 5 .3 12 .8 5 .,9 -7 .3 -2 .8 -23 .3 -21 .0 -7 .2 -22 .0 -9 .9 -11 .6 -0 .6 -10 .8 29 .6 -9 .6 -6 .1 1 .1 -4 .6 -2 .3 -3 .9 -6 .0 11 .7 -1 .8 -2 .1 3 .6 7 .8 10 .6 23 .4 18 .0 17 .0 -8 .3 8 .8 10 .8 1 .3 11 .3 14 .8 8 .8 10 .1 9 .4 14 .3 4 .5 11 .9 14 .6 16 .8 -1 .8 7 .5 12 .4 16 .7 13 .2 15 .4 -3 .7 17 .6 30 .8 17 .1 20 .1 16 .2 16 .6 22 .1 17 .9 15 .7 14 .7 12 .6 21 .9 10 .8 10 .4 9 .9 7 .2 14 .0 13 .4 10 .5 11 .3 12 .6 22 .0 -8 .4 7 .3 7 .4 6 .5 12 .5 -0 .5 -7 .7 4 .8 9 .0 9 .5 9 .2 4 .3 17 .7 20 .9 7 .6 22 .6 12 .9 13 .9 22 .9 11 .4 8 .9 11 .0 -5 .4 22 .3 23 .7 25 .3 20 .2 22 .5 -15 .6 23 .4 20 .8 13 .6 15 .9 24 .2 14 .9 32 .3 26 .4 17 .1 20 .0 14 .7 DuPont-6515 16-:18 24 .9 23 .9 28 .7 27 .1 27 .4 29 .9 35 .4 37 .5 32 .0 27 .9 25 .6 35 .1 27 .1 34 .4 27 .6 35 .1 37 .0 34 .4 24 .6 22 .6 33 .3 24 .1 -57 - Company t.o.HnytconlnTSCA cm H-24768: Developmental Toxicity Study in Rats INDIVIDUAL BODY W E I G H T CHANGES (grams) G R O U P III: 100 M G / K G / D A Y ANIMAL NUMBER 18-20 20-21 DAYS OF GESTATION 6-21 6-21a 648519 648521 648527 648530 648533 648543 648545 648548 648550 648557 648558 648568 648569 648572 648578 648581 648593 648594 648595 648599 648603 648604 40 ,.9 42 .2 26 ,.7 38 ,.1 45 .,0 31..0 32 .9 34 .9 46 .7 39.,1 28 .,2 41 .0 24 ,.0 21 ,.6 26 .2 41 .4 35 ,.2 49 ,.3 38 ..6 29 ..2 26 ..3 29 ..9 19..2 20..8 22 ,.0 18,.1 18..5 15 ,.1 21,.9 34 ,.8 27,.5 14 ,.9 6 .6 34 ,.4 30 .2 27..8 32 ,.8 21,.8 16 .3 21..1 18 .7 20 ,.4 24 .0 16 ,.8 135,.6 130,.6 114 ,.4 109.,6 104,,5 106.,1 137..3 158.,3 155.,8 121.,0 103 .,6 155.,8 130..8 132.,1 134.,0 150..9 139..9 177..0 154 ..3 115..5 135..9 128..8 48 .2 22 .8 43 .6 15,.5 12 .2 12 ,.6 37 .8 55 ,.4 41,.8 27 .8 33 ,.1 61,.2 35 .4 34 ..8 45 .,2 52 ,.3 34 ,.9 57..4 77 ,.4 32 ..1 49..4 43 ..9 DuPont-6515 DoM not contain T * company Sar,WKld -58- H-24768: Developmental Toxicity Study in Rats DuPont-6515 INDIVIDUAL BODY WEIGHT CHANGES (grams) G R O U P IV: 400 M G / K G / D A Y ANIMAL NUMBER 4-6 6--8 DAYS OF GESTATION 8-10 10-12 12-14 14-16 648523 648525 648526 648532 648534 648539 648540 648552 648555 648556 648560 648561* 648563 648570 648577 648579 648583 648584 648586 648589 648590 648597 18 .,1 16..8 11..9 25 .8 9 .2 8 ..9 17 ..9 9,.9 13 .7 2 .8 2 .6 4 ,.5 6..4 1..7 6 .7 5 .4 9 .8 12 ..0 10 ..8 8 .3 14 .2 3 .4 -9..3 -3 ..8 -30.,4 -31..7 -25.,5 -34.,3 -40 .,6 -20,.7 -32 .7 -21..6 -23 .5 -21..7 -10,.1 -9..4 -21..4 -12 .5 -11..6 -26 .1 -22 .4 -23 .0 -17 .9 -29 .3 6. 7 11. 2 4 .1 -14 .3 0. 6 -4. 1 -2. 9 -0..1 6 ..7 0..3 16..2 9.,2 1.,0 9..8 13 .,2 10 ..7 5 .,6 1.,2 11.,3 12..0 11..3 0..9 5 ,.6 5 .1 17 .9 -1,.1 16 .3 14 .0 10 .8 3 .8 6 .5 16 .1 9 .7 0 .0 10 .0 13 .5 2 .0 17 .6 11 .5 17 .2 3 .2 7 .2 21..9 23 .1 11..0 2 ,.5 9,.8 24 .4 15 ,.9 4 ,.5 11 .4 3 ,.6 -2 .,1 9..7 10..9 -5 .1 15..5 -0 .7 9 .8 11 ,.9 -10 .4 2 .0 -0 .,9 11..3 1..0 7.,6 7 .6 10 .7 11 .6 1 .6 16 .5 9 .3 -2 ,.7 24 .5 8 .6 7 .9 -1 .2 4 ,.9 2 .2 2 .1 10 .1 10 ,.7 5 .7 16 .0 20.,9 14,.8 7..1 10 ..7 16-18 27 .5 35 .5 26 .2 6,.8 18,.2 19..0 25 ..5 17..3 29 .6 26,.3 28 .4 10 .2 24 ..1 19,.0 38 ,.1 23 .,2 35 .,5 27.,7 44 ..9 31..5 23 ..6 26 ..9 - 5 9 - TJBtBP tS C A cSI Ooe* TVO*con'altl H-24768: Developmental Toxicity Study in Rats INDIVIDUAL BODY WEIGHT CHANGES (grams) G R O U P IV: 400 M G / K G / D A Y ANIMAL NUMBER 18-20 20-21 DAYS OF GESTATION 6-21 6- 21a 648523 648525 648526 648532 648534 648539 648540 648552 648555 648556 648560 648561 648563 648570 648577 648579 648583 648584 648586 648589 648590 648597 30 .1 41..8 33 ,.3 15 .,1 33 ,.4 46 ,.4 36 ,.4 28 .4 40 ,.4 38 ..3 28 ..0 11..5 26 .1 14 .,5 29..1 34 .2 18 ..3 31..7 29..8 27 ,.8 21..8 31. 1 27 .1 14 .4 18 .3 33 .0 11 .7 14 .7 18 .0 20 .0 22 .4 14 .3 15..7 8 .8 20 .1 25 .6 23 ,.7 19 .7 7 .2 13 .4 13 .3 14 .7 15 .7 16 .0 106..3 117 ,.4 90..8 33 ,.8 87 .1 69..5 55 .9 76 .,8 79..4 91..3 84 .2 17..8 88..9 74 ,.4 104 ..6 115 .5 61..8 83 .1 100..1 96 .3 84 .5 87 ,.0 6 .9 17,.5 3 ,.6 - -40..3 -4 .5 -10..8 -21..0 8..2 -0 ,.7 11..1 4 ,.0 -- 17..4 -0 .8 14 .,6 -0 ,.6 1,.9 -1..5 10..0 6 .2 -2 .3 9,.4 DuPont-6515 -60- H-24768: Developmental Toxicity Study in Rats DuPont-6515 APPENDIX C Individual Food Consumption 61 C9B1p a n ,^ o ! 1DoM contain U A C B I H-24768: Developmental Toxicity Study in Rats Individual Food Consumption Explanatory Notes Footnotes a Pregnant by stain. Data excluded from the calculations. b Due to technician error, food consumption was not recorded on day 8G. Abbreviations -----= No Data DuPont-6515 -62- w)lc.orfa'"t S H-24768: Developmental Toxicity Study in Rats DuPont-6515 GROUP I : 0 MG/KG/DAY ANIMAL NUMBER 4--6 648517 648520 648522 648528 648535 648536 648544 648549 648553 648554 648559 648566 648567 648571 648573 648576 648582 648587 648588 648592 648601 648602 23 ,.4 2 .4 21..7 25 .7 21..5 21..9 22..0 21..2 21..4 25,.4 24 .,4 24 .4 22 ,.0 24 ..9 25..2 22 ..0 24 ..9 20 .1 21,.8 24 ..2 24 ,.2 20..9 INDIVIDUAL FOOD C O N S U MPTION (grams) 6--8 25 .9 15 .3 26 .4 25 .9 21 .1 21 .9 23 .6 20 .9 19 .7 29 .5 25 .2 25 .8 21 .2 23 .4 25 .3 23 .4 23 .9 20 .9 20 .9 24 .5 22 .4 22 .6 DAYS OF GESTATION 8-10 10-12 12-14 26 .2 28 .0 25 .7 24 .8 21 .8 22 .3 23 .8 23 .9 22 .3 27 .7 23 .7 22 .3 20..6 24 .1 22 ,.6 23,.3 25.,8 23 .,4 22 .6 25..1 24..9 21..3 27 .0 31 .6 25 .4 23 .0 20 .6 25 .0 27 .4 21 .7 24 .6 28 .3 25 .0 24 .1 23 ,.4 22 .7 24 ,.3 26.,6 26.,5 23 ..8 23 .8 25 .,3 26..6 26.,7 26..9 27..5 29 .3 25..9 23 .1 25 .6 31 .2 23 .5 26 .9 30 .2 25 .4 24 .0 25 .4 26,.1 26 .1 27 .3 28 .3 26 .3 28 .4 28 .9 30..9 25 .0 14-16 27..9 2 .2 28..3 28..9 22..7 26 .4 32 .7 26..6 27..5 33 .2 28..2 23 .9 31,.8 29..6 27 ,.5 26..9 28 ..9 25 .3 30,.1 36..1 30..6 30..4 16-18 25 ,.9 34 ..0 30 .9 30..1 25 .0 27 .1 36 .0 30 ,.0 33 .2 38 .8 29..3 24 .8 28 ,.5 31 ,.6 33 ,.4 26..8 28 ..1 28 .9 27 .4 31,.2 32 .7 27 .9 -63- CpnPanttJI=sfe TSCA CBi H-24768: Developmental Toxicity Study in Rats GROUP I: 0 MG/KG/DAY ANIMAL NUMBER 18-20 INDIVIDUAL FOOD CONSUMPTION (grams) DAYS OF GESTATION 20-21 6-21 648517 648520 648522 648528 648535 648536 648544 648549 648553 648554 648559 648566 648567 648571 648573 648576 648582 648587 648588 648592 648601 648602 28 .8 36 .4 29,.7 28,.6 24 ,.8 26,,1 32 ,.3 27 ,1 28 ,3 29,.8 31 .7 24 .3 28,.1 28,.2 28,.5 26..3 32 .1 25 .,0 26 .,9 30 ,.3 31,,3 28 .,5 27 .9 33 .3 28 .5 32 .1 21 .9 26 .7 31 .9 24 .9 26 .8 35 .7 23 .9 23 .9 25 .7 25 .9 24 ,.6 22 ,.4 30,.0 22 ..2 21..9 27 .9 28 .8 31..2 27 .0 25 .5 28 .0 27 .1 22 ,.7 25 ,.0 29..7 24 ,.8 26 .1 31 .4 26,.7 24 ,.1 25,.6 26..5 26..7 25.,6 27.,8 24 .,6 25..4 28 ..7 28 ..5 26 ..4 DuPont-6515 -64- H-24768: Developmental Toxicity Study in Rats G R O U P II: 50 M G / K G / D A Y ANIMAL NUMBER 4--6 INDIVIDUAL FOOD C O N S U M P T I O N (grams) 6--8 DAYS OF GESTATION 8-10 10-12 12-14 648518 648524 648529 648531 648537 648538 648541 648542 648546 648547 648551 648562 648564 648565 648574 648575 648580 648565 648591 648596 648598 648600 22..6 23 .9 26 .2 22 .3 19 .7 23 .4 23 .4 26 .8 26 .5 26 .6 22 .6 24 .0 27 .4 21..1 26 ..6 26 .3 24 .6 24 .1 20 .3 22 .4 20 .2 23 ,3 17 .6 21..5 19 .6 18 .8 22 .2 17 .6 15 .3 26 .1 20 ,.6 22 ,.3 17 ,9 15 .6 23 ,.3 16 .9 27..5 22 .1 23 .9 19 .7 19 .1 18 .6 19 .9 17..1 20..3 23 ..4 17..5 22..1 22..1 22..0 18..0 28..1 23 ..9 25 .9 19.,8 19 ..8 25. 3 17. 9 28. 1 20 .8 23 .8 21..6 19..0 17..4 19..0 16..2 21,.9 25,.6 22 .7 22 .6 27 .2 21,.0 21,.1 27 ,.4 24 .,3 27 .6 21 ,.7 22 ..4 29..4 20..3 30..0 24 .8 30.,7 26 .3 23 ,.8 23 ..0 21..6 24 .,9 22 .5 27..6 23 .4 23 .6 27,.3 24 ,.9 24 .4 28 .3 28 ..7 28 .7 25 .2 25 .8 29..8 21,,7 30 .,1 26 .,1 27.,3 32 .8 28 ..1 25 ..3 22 .7 28 .7 14-16 23 ,.4 30,.1 28..5 24..7 28 ,.9 25 .6 24..0 30..2 30 .4 31 .4 24,.9 26,.7 35..5 24 .4 33 ..9 26 ..6 29..9 30 .6 25,.9 24 .,9 22 .,0 26 .,8 DuPont-6515 16-18 26..3 30..2 34 .7 30 .8 31 .9 28 .2 30 .2 33 ,.0 31..7 32 .4 28 .3 30 .1 34 .8 27 ,.4 35 ..3 28 .3 31,.9 32 .9 24 .8 29 .9 23 ,.1 28 .1 -65 - QOBS 00^' pgfltpanU StowS P * * t s c ^ cB' H-24768: Developmental Toxicity Study in Rats INDIVIDUAL FOOD CONSUMPTION (grams) GROUP II: 50 MG/KG/DAY ANIMAL NUMBER 18-20 DAYS OF GESTATION 20-21 6-21 648518 648524 648529 648531 648537 648538 648541 648542 648546 648547 648551 648562 648564 648565 648574 648575 648580 648585 648591 648596 648598 648600 25.6 28.8 27.2 25.3 28.7 28.4 30.8 33.3 30.6 30.9 28.5 31.7 33.4 27.4 29.6 27.7 28.3 31.1 27.1 28.2 21.1 26.9 29.2 28.8 29.1 21.8 28.1 24.1 17.4 26.0 25.0 32.9 24.9 26.3 31.5 18.9 29.5 22.7 25.9 27.3 22.7 32.6 20.1 29.4 22.9 26.9 25.1 23.8 27.0 24.0 23.0 29.2 27.0 28.8 23.8 24.7 30.3 22.1 30.6 25.0 27.8 27.8 23.9 24.5 21.3 24.4 DuPont-6515 -66- a D oes not contain TSCA CBl pompany Sanitizfid* P H-24768: Developmental Toxicity Study in Rats INDIVIDUAL FOOD CO N S U M P T I O N (grams) G R O U P III: 100 M G / K G / D A Y ANIMAL NUMBER 4-6 6-8 DAYS OF GESTATION 8-10 10-12 12-14 648519 648521 648527 648530 648533 648543 648545 648548 648550 648557 648558 648568 648569 648572 648578 648581 648593 648594 648595 648599 648603 648604 26.5 24.9 24.1 22.4 22.6 28.9 22.4 23.2 26.3 25.8 6.4 26.1 25.2 25.0 25.7 28.8 22.0 24.1 16.1 22.1 24.8 10.8 18.0 22.2 9.6 10.9 18.2 14.3 15.9 14.3 21.3 16.4 20.4 22.2 20.3 19.9 17.9 17.1 22.8 18.7 22.6 19.9 19.5 18.1 19.9 20.8 21.5 16.8 22.4 10.7 19.6 22.7 19.9 23.8 29.3 23.1 20.7 23.1 20.8 18.7 20.8 20.0 23.4 15.5 18.2 21.7 25.6 25.4 21.0 12.9 23.9 21.4 20.1 23.3 24.2 21.4 28.6 24.9 24.2 25.3 25.9 26.0 25.1 26.7 25.1 18.7 22.0 22.4 25.8 25.8 28.8 20.1 17.3 24.5 21.0 25.7 28.2 22.7 20.2 25.4 24.8 24.7 30.4 23.8 26.4 28.6 25.3 24.3 26.2 23.9 14-16 30.4 25.0 26.3 23.8 11.1 26.1 25.1 27.1 29.2 26.2 7.1 29.9 26.9 29.1 32.6 27.3 16.1 30.9 36.3 25.5 25.8 24.6 DuPont-6515 16-18 31.2 30.0 30.0 28.8 17.2 28.4 29.9 29.3 29.6 30.6 11.9 32.1 26.6 28.8 26.9 31.8 26.8 32.4 30.4 26.1 28.9 25.9 -67- t S C A CB' n0t c o ^ am pgmpany. Saw^ f e U . P 0 6 8 H-24768: Developmental Toxicity Study in Rats INDIVIDUAL FOOD CONSUMPTION (grams) GROUP III: 100 MG/KG/DAY ANIMAL NUMBER 18-20 DAYS OF GESTATION 20-21 6-21 648519 648521 648527 648530 648533 648543 648545 648548 648550 648557 648558 648568 648569 648572 648578 648581 648593 648594 648595 648599 648603 648604 31 .8 30 .8 29 .0 25 .1 27 .7 28..2 26 .4 29..4 30..1 27,.5 19 .8 34 .7 28 .4 26..1 27.,0 34 ..6 26 ..8 34 ..0 31..3 23 ..9 25..8 22 ..7 29,.8 25..3 26 .5 20..9 27..6 16,.2 25 .0 28,.6 34 ,.4 23 .0 20 .6 33 .0 23 .3 27 .2 20 .8 28 .,4 24 .1 31,.2 23 ,.0 27 ,.8 30 ,.6 23 .3 26 ,.4 25..7 23 .9 19,.9 20 ,.2 21,.6 22 .7 24 ,.8 26..6 24..0 19,.7 27..9 24 .5 25 .4 25..6 25..8 23 .6 27 .6 27 ,.4 22 ,.4 24 ,.2 22 .8 DuPont-6515 -68- n ot c o n ta '11T S C A C l H-24768: Developmental Toxicity Study in Rats DuPont-6515 G R O U P IV: 400 M G / K G / D A Y ANIMAL NUMBER 4--6 I N DIVIDUAL FOOD CO N S U M P T I O N (grams) 6--8 DAYS OF GESTATION 8-:L0 10-12 12-14 648523 648525 648526 648532 648534 648539 648540 648552 648555 648556 648560 648561a 648563 648570 648577 648579 648583 648584 648586 648589 648590 648597* 27 .3 14 .2 21 .0 28 .6 26 .5 27 .1 25..2 28..1 24 .0 20 .8 25 .6 19.,7 27 .9 24 .1 23 ,.4 24 .3 23 .5 24 ,8 23 ,.4 22 ,.3 21,.6 22 ..4 18 .5 15 .3 4 .7 7 .0 10 .5 6 .3 3 .4 11 .1 3 .5 8 .1 12 .0 7 .4 12 .0 14 .2 7 .2 15 .1 12 .8 6 .8 9 .7 9 .8 14 .9 -- 15 .3 17 .9 8 .9 6 .2 11 .6 10 .8 9 .1 14 .6 10 .1 10 .9 20 .4 10 .6 13 .7 17 .3 18 .8 16 .2 14 .0 11 .4 15 .5 14 .8 18 .0 15 ..9 13 ,.5 16 ,.9 5 ,.4 17 ,.6 17 ,.3 15 ,.1 15 .,5 16 .8 17 ,.4 19.,8 10 .,7 17 .2 20..4 14 ..5 21..6 18 .9 17 ,6 17 .5 18 .9 23 .4 17 .8 22 .0 16 .9 18 .8 18 .6 20 .5 16 .8 17 .4 17 .6 11 .9 17 .5 22 .2 11.,9 22 .4 20 .6 19 .7 18..6 16 .4 15 .5 19 .7 21 .1 19 .4 16 .2 14-16 20 .6 18 .4 19 .8 14 .3 24 .0 18 .9 12 .4 26 .4 15 .5 21 .8 17..2 12 .1 17 .7 21 .6 19,.2 21 .6 16 .8 20 .4 25 .9 22 .2 23 .3 13 .9 16-18 26 .3 27 .4 19 .3 13 .8 22 .9 26 .1 16 .6 23 .9 22 .3 24 .3 22,.3 12 .,4 24 ,.6 18 ,.0 24 ..4 22 .9 30 .6 27 .7 30 .6 26,.1 20 .7 22 .3 pg yri p a n y a a n H teodi nolCft!tfa ^n T S C f t H-24768: Developmental Toxicity Study in Rats INDIVIDUAL FOOD CONSUMPTION (grams) GROUP IV: 400 MG/KG/DAY ANIMAL NUMBER 18-20 DAYS OF GESTATION 20-21 6-21 648523 648525 648526 648532 648534 648539 648540 648552 648555 648556 648560 648561 648563 648570 648577 648579 648583 648584 648586 648589 648590 648597 26 .3 33 .8 26..8 16 .3 23 ,.6 30..5 25 ..8 28..5 29 ..1 26 .,4 27 .3 18 ..6 28 ..8 21..2 26 ..4 30 .,1 24 .6 26 .6 28 .0 23 .0 21..5 27 .,3 25 .6 23 .1 20 .8 37 .0 22 .2 19..1 19..4 27 .1 24 .2 18 .4 27 .1 18 .6 23 .2 19 .9 21..5 27 ,.9 22 ,.7 22 ,.5 23 .0 22 ..4 22 ..8 24 ,.4 21..0 20,.6 16 .7 13 ,.3 18 .9 18..2 14 ,.6 20 .2 16,.2 18 ,.1 20.,6 12 .4 19..7 19,.1 18 ,.8 21,.3 19 .4 18 ..3 21..1 19 ..6 20,.4 16 ,.6 DuPont-6515 -70- H-24768: Developmental Toxicity Study in Rats DuPont-6515 APPENDIX D Individual Clinical Observations not contain TSCA CBl Company, Sanitized. D oes -71 - H-24768: Developmental Toxicity Study in Rats Individual Clinical Observations DuPont-6515 Explanatory Notes Footnotes a The first observation recorded each day is indicated by "a"; the second by "b". Observations were made twice daily on days 6-20G. If no signs were observed during the study examinations, the "b" entries are omitted from the printout. not contain T S C A C B Company Sanitized. D oes -72- H-24768: Developmental Toxicity Study in Rats G R O U P I: 0 M G / K G / D A Y ANIMAL NUMBER: OBSERVATION Sanitized. Does not contain <5 i TJ 3 < H (O O > o on 648517 ALOPECIA RIGHT FRONT PAW ALOPECIA RIGHT FRONT LEG SACRIFICED BY DESIGN 05/21/01 648520 SACRIFICED BY DESIGN 05/21/01 648522 SACRIFICED BY DESIGN 05/21/01 648528 SACRIFICED BY DESIGN 05/21/01 648535 SACRIFICED BY DESIGN 05/21/01 648536 SACRIFICED BY DESIGN 05/21/01 648544 SACRIFICED BY DESIGN 05/22/01 648549 SACRIFICED BY DESIGN 05/22/01 648553 SACRIFICED BY DESIGN 05/22/01 648554 SACRIFICED BY DESIGN 05/22/01 INDIVIDUAL CLINICAL OBSERVATIONS3 DAYS OF GESTATION ON WHICH SIGN WAS OBSERVED 4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21 a : , ,6,7,8,9,10,11,12,13,14,15,16,17,18, b: , , 6 , 7 , 8 , 9 , 1 0 , 1 1 , 1 2 , 1 3 , 1 4 , 1 5 , 1 6 , 1 7 , 1 8 , a: t i f i l i ///// Il II b: t i f i l i I , l I ! ! I ,18, , a: I I I I I l I I I I I / I / / I I , ,21 ^ I I I i I I I / / I I I t I I I i 21 a: I I I ! I t i l i , ,21 3 l I I II t ! t I I I ! ! I l I I2 1 3 ! I l I I ! / / , I l I I I I I I21 3 ! I l I I ! t ! , ! ! ! I ! I I 21 3 / , 2 1! I l II ! ! ! t ! ! !!Il ^ ! I l I I ! ! ! , / ! I / I I ! ,21 / / /! I l II ! f ! ! I I I I I21 filili t I , , ! ! / / / ! I 21 -73- DuPont-6515 ) H-24768: Developmental Toxicity Study in Rats GROUP I : 0 MG/KG/DAY ANIMAL OBSERVATION NUMBER : 648559 SACRIFICED BY DESIGN 0 5/ 2 2 /0 1 648566 SACRIFIC ED BY DESIGN 05/ 2 3 /0 1 648567 SACRIFIC ED BY DESIGN 0 5/ 2 3 /0 1 648571 ALOPECIA RIGHT SIDE SACRIFICED BY DESIGN 0 5/ 2 3 /0 1 648573 SACRIFIC ED BY DESIGN 0 5/ 2 3 /0 1 648576 SACRIFIC ED BY DESIGN 0 5/ 2 3 /0 1 648582 SACRIFIC ED BY DESIGN 0 5 / 2 3 /0 1 648587 SACRIFIC ED BY DESIGN 0 5/ 2 4 /0 1 648588 SACRIFICED BY DESIGN 0 5 / 2 4 /0 1 648592 SACRIFIC ED BY DESIGN 0 5/ 2 4 /0 1 ) IN D IVID U A L C LIN IC A L OBSERVATIONS3 4 D, A5 Y, S6 , O7 F, 8G, 9ES, 1TA0 T, I1O1N, 1O2N, 1W3 ,H1IC4H, 1S5I,G1N6 , W1 A7S, 1O8 B, 1SE9R, V2E0D, 2 1 a : 1 i 1 1 f 1 1 1 1 1 1 1 1 , , , ,21 a : , t 1 1 t 1 1 / I I I I / , , , ,21 a : 1 f t t 1' 1 1 t t 1 1 1 1 , , , , 2 1 a: b: a: I 1 / / i' / 11<111 1 1 / / 1' r 1 1 i 1 1 I , , 1 3 , , 1 1 4 4 , , 1 1 5 5 , , 1 1 6 6 , , 1 1 7 7 , , 1 1 8 8 , , 1 1 9 9 , , 2 2 0 0 ,2 , 1 I I I I / , , , ,21 a : 1 1 / 1 1' f 1' > I I I 1 1 , , , , 2 1 a : 1 1' t r i' I 1' / ! / ! 1 ! , , , , 2 1 a : t ,' 1 l t 1 .t i , , . 1 / , , , , 2 1 a : / jr t i r I i' 1 I l l / / , , , , 2 1 a : ! ir r i 1 / 1f ! I I I / 1 i , , 2 1 a : t i' l l , t 1 1f 1 I I I / / , , , , 2 1 ) DuPont-6515 Cpmpany Sanitized. Does not contain TSCA CBI -74- H-24768: Developmental Toxicity Study in Rats G R O U P I: 0 M G / K G / D A Y ANIMAL NUMBER: OBSERVATION 648601 ALOPECIA LEFT HIND QUARTERS ALOPECIA LEFT SIDE SACRIFICED BY DESIGN 05/24/01 648602 SACRIFICED BY DESIGN 05/24/01 INDIVIDUAL CLINICAL OBSERVATIONS'3 DAYS OF GESTATION ON WHICH SIGN WAS OBSERVED 4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21 a : ,9,10,11,12,13,14,15,16,17,18,19,20,21 b: ,9,10,11,12,13,14,15,16,17,18,19,20, a : , , , , , , / / / , i ,20,21 b: , 2 0 , a : ,21 ,21 DuPont-6515 SCompanj Sanitized. Does 3a o o3 2. 5` -4 ton > oCO -75- Company Sanitized. Does not contain TSCA CB1 H-24768: Developmental Toxicity Study in Rats G R O U P II: 50 M G / K G / D A Y ANIMAL NUMBER : OBSERVATION 648518 SACRIFICED BY DESIGN 05/21/01 648524 SACRIFICED BY DESIGN 05/21/01 648529 SACRIFICED BY DESIGN 05/21/01 648531 SACRIFICED BY DESIGN 05/21/01 648537 ALOPECIA LEFT FRONT PAW SACRIFICED BY DESIGN 05/21/01 648538 SACRIFICED BY DESIGN 05/21/01 648541 ALOPECIA LEFT HIND QUARTERS ALOPECIA ABDOMINAL SACRIFICED BY DESIGN 05/22/01 648542 SACRIFICED BY DESIGN 05/22/01 648546 SACRIFICED BY DESIGN 05/22/01 648547 SACRIFICED BY DESIGN 05/22/01 INDIVIDUAL CLINICAL OBSERVATIONS3 DAYS OF GESTATION ON WHICH SIGN WAS OBSERVED 4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21 a: I I I I I I 1 III , , ................. 2 1 a: 1 l 1 I I I ! 1 1 1 , , , , , , ,21 a: 1 I / I l l / til / / / / / i 12 1 a: I I I I I I ! / / I t / / / / i t2^ 1a a: I I I I l l b: I I I I I I a: ! / / I l l 1 III , , ,17, , , , ! III , ,16,17, , , , I ! 1 f / / 1 1 ! 1 12*'1*- a: / t 1 I I I 1t 1! i t i i / / 21 a: ! i 1 I I I b: I I I I l l a: 1 1 1 b: I I I I I I a: 1 1 1 I I I ! Ill , ,16,17,18,19,20,21 1 III , ,16,17,18,19,20, 1 1 1 , , ,17,18,19,20,21 1 1 1 1 , ,16,17,18,19,20, 1 III / t ! I 1 ! ! 2**1 a: I I I I I I 1 III / / ! t I ! f 2i 1A. a: I I I I I I / 1 1 1 i i i / i i /21 a: I I I I I I / III i i i i i i /21 -76- DuPont-6515 'Company Sanitized. Does not contain TSCA CBI ) H-24768: Developmental Toxicity Study in Rats ) G R O U P II: 50 M G / K G / D A Y ANIMAL NUMBER: OBSERVATION 648551 ALOPECIA ABDOMINAL SACRIFICED BY DESIGN 05/22/01 648562 SACRIFICED BY DESIGN 05/23/01 648564 ALOPECIA BOTH FRONT LEG SACRIFICED BY DESIGN 05/23/01 648565 SACRIFICED BY DESIGN 05/23/01 648574 SALIVATION SACRIFICED BY DESIGN 05/23/01 648575 SACRIFICED BY DESIGN 05/23/01 648580 SACRIFICED BY DESIGN 05/23/01 648585 ALOPECIA BOTH FRONT LEG SACRIFICED BY DESIGN 05/24/01 648591 SACRIFICED BY DESIGN 05/24/01 INDIVIDUAL CLINICAL OBSERVATIONS3 DAYS OF GESTATION ON WHICH SIGN WAS OBSERVED 4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21 a: , , , , , 9 , 1 0 , 1 1 , 1 2 , 1 3 , 1 4 , 1 5 , 1 6 , 1 7 , 1 8 , 1 9 , 2 0 , 2 1 b: , , , , , 9 , 1 0 , 1 1 , 1 2 , 1 3 , 1 4 , 1 5 , 1 6 , 1 7 , 1 8 , 1 9 , 2 0 , 3 /I l 1t t i i i i i i I f tt 1I 21 ! tiltil ! 1 i / t 1 t 1 t r /21 3. r t r / t r i / i t i t i i / # 2 0 , 2 1 to* t i l t i l /I 1 ! 1 1 1 i l i2 0 , 3; i r i i t r ; i / i i i i i t ;21 3 I / t 2 1! I l 11 ! ! 1 ! ! !!I!1 3 II II tt ! / ! / / / ! ( // 3 / / 2 1I I t II l 1 1 1I ! 1 1 1! 3I lilil / 2 1! ! 1 1 t 1 t 1 ! t 3 * / / 2 11 1 1 1 I 1 ! 1 1 1 1 1 1 1! 3 ! / f 2 1i i i ii t t r t i i i i i 12 0 to : i t f f t # # # # # , # # i f / 2 0 # 3 / / / / t I I II ! !!1t1 1 1 21 3 ! I l I I ! ! / / / / ! / / f / / 21 -77- DuPont-6515 ) H-24768: Developmental Toxicity Study in Rats G R O U P II: 50 M G / K G / D A Y ANIMAL NUMBER: OBSERVATION INDIVIDUAL CLINICAL OBSERVATIONS'9 DAYS OF GESTATION ON WHICH SIGN WAS OBSERVED 4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21 648596 ALOPECIA RIGHT FRONT PAW STAIN CAGEBOARD RED SACRIFICED BY DESIGN 05/24/01 a : , ,6,7,8,9,10,11, ,13,14, / I , ,19,20,21 b: , , 6 , 7 , 8 , 9 , 1 0 , 1 1 , 1 2 , 1 3 , 1 4 , l ! , ,19,20, a: 1 1 1 1 1 1 1 l 1 1 t 1 t ( I I I b: i r / / / / r / t 1*-2->/ / I 1 ! I I ! a: t i f i t i ! / / I 1 / I i i i /21 648598 SACRIFICED BY DESIGN 05/24/01 a : 1 1 1 I 1 I / / / ! 1 1 / , , , ,21 648600 SACRIFICED BY DESIGN 05/24/01 a fi O 3 T 21 ) DuPont-6515 Sanitized. Does -78- Company Sanitized. Does not contain TSCA CBI H-24768: Developmental Toxicity Study in Rats ) INDIVIDUAL CLINICAL OBSERVATIONS'3 G R O U P III; 100 M G / K G / D A Y ANIMAL NUMBER : OBSERVATION =======:======:== DAYS OF GESTATION ON WHICH SIGN WAS OBSERVED 4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21 648519 SACRIFICED BY DESIGN 05/21/01 ,21 648521 SACRIFICED BY DESIGN 05/21/01 ,21 648527 ALOPECIA BOTH FRONT PAW ALOPECIA RIGHT SIDE ALOPECIA LEFT HIND QUARTERS ALOPECIA BOTH HIND QUARTERS ALOPECIA BOTH SIDE ALOPECIA LEFT FRONT LEG ALOPECIA BOTH FRONT LEG STAIN PERINEUM YELLOW ALOPECIA ABDOMINAL SACRIFICED BY DESIGN 05/21/01 a : ,6,7, , 9 , 1 0 , 1 1 , 1 2 , 1 3 ,14,15,16, 1 7 , 1 8 , 19,20,21 b: ,6,7, , 9 , 1 0 , 1 1 , 1 2 , 1 3 , 1 4 , 1 5 , 1 6 , 1 7 , 1 8 , 1 9 , 2 0 , a: , , , ,9,10, , , , , , , ,, b: ,,,,9,10, ,,,,,,,, a: ,,,,9, , , , , , , , ,, b: ,,,,9, , , , , , , , ,, a: , , , ,, 1 0 , 1 1 , 1 2 , 1 3 , 1 4 , 1 5 , 1 6 , 1 7 , 1 8 , 1 9 . 2 0 . 2 1 b: , , , ,, 1 0 , 1 1 , 1 2 , 1 3 , 1 4 , 1 5 , 1 6 , 1 7 , 1 8 , 1 9 . 2 0 , a : , , , ,, , 1 1 , 1 2 , 1 3 , 1 4 , 1 5 , 1 6 , 1 7 , 1 8 , 1 9 . 2 0 . 2 1 b: , , , ,, , 1 1 , 1 2 , 1 3 , 1 4 , 1 5 , 1 6 , 1 7 , 1 8 , 1 9.20, , , ,, ,a : tt!t! I r ! !4 4 18 19.20 . 2 1 b: a: b: tttti ,,t t i i - i ti iit i i ii i ,i i t i , 1 5 , 1 6 , 1 7 ,i i i , 1 4 , 1 5 , 1 6 , 1 7 i 19.20, , , a: b: ,15, a : , ,17,18, 19,20,21 b: , 1 6 , 1 7 , 1 8 , 1 9 , 2 0 , a : , ,21 648530 SACRIFICED BY DESIGN 05/21/01 ,21 648533 SACRIFICED BY DESIGN 05/21/01 ,21 648543 SACRIFICED BY DESIGN 05/22/01 ,21 -79- ) DuPont-6515 g ^ p a n y Sanitized. Does not contain TSCA CBI ) H-24768: Developmental Toxicity Study in Rats ) G R O U P III: 100 M G / K G / D A Y ANIMAL NUMBER: OBSERVATION 648545 ALOPECIA LEFT SHOULDER ALOPECIA RIGHT FRONT LEG ALOPECIA ABDOMINAL ALOPECIA NECK ALOPECIA RIGHT FRONT PAW ALOPECIA BOTH FRONT LEG ALOPECIA RIGHT REAR LEG SCAB RIGHT FRONT LEG SACRIFICED BY DESIGN 05/22/01 648548 ALOPECIA BOTH FRONT PAW ALOPECIA BOTH FRONT LEG ALOPECIA RIGHT REAR LEG ALOPECIA BOTH REAR LEG ALOPECIA ABDOMINAL SACRIFICED BY DESIGN 05/22/01 648550 SACRIFICED BY DESIGN 05/22/01 INDIVIDUAL CLINICAL OBSERVATIONS3 DAYS OF GESTATION ON WHICH SIGN WAS OBSERVED 4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21 a: b: , 6 , a: b: a: b: a: b: a: b: a: b: a: b: a: b: a: a: b: a: b: a: b: a: b: a: b: a: / / /11 J- t /trI tr t l T1 , , , , , , , , , , ,11,12,13,14,15,16,17,18,19,20,21 ,11,12,13,14,15,16,17,18,19,20, ,11,12,13,14,15,16,17,18,19,20,21 ,11,12,13,14,15,16,17,18,19,20, , ,12,13,14,15,16, , ,, , , ,12,13,14,15,16, , ,, , , , , ,14,15,16, , , ,20,21 ,, , ,14,15,16,17, , ,20, ,, , ,14,15,16,17,18,19, , ,, , ,14,15,16,17,18,19, , ,17, ,21 ,14,15,16,17 ,14,15,16,17 iiit , , , ,17 18.19, 18.19, ,20,21 , 20, ,20,21 ,20, , ,21 ,21 -80- ) DuPont-6515 C om pany San itized . D o e s not con tain TSCA CB H-24768: Developmental Toxicity Study in Rats GROUP III: 100 M G / K G / D A Y ANIMAL NUMBER: OBSERVATION INDIVIDUAL CLINICAL OBSERVATIONS3 DAYS OF GESTATION ON WHICH SIGN WAS OBSERVED 4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21 648557 SALIVATION SACRIFICED BY DESIGN05/22/01 a: a: 648558 SALIVATION DISCHARGE VAGINAL OPENING BROWN SACRIFICED BY DESIGN05/22/01 a: b: a: b: a: 648568 SALIVATION SACRIFICED BY DESIGN05/23/01 a: b: a: 648569 SACRIFICED BY DESIGN 05/23/01 a 648572 ALOPECIA LEFT FRONT LEG ALOPECIA BOTH FRONT LEG ALOPECIA BOTH HIND QUARTERS ALOPECIA BOTH SIDE ALOPECIA ABDOMINAL ALOPECIA RIGHT FRONT PAW SALIVATION SACRIFICED BY DESIGN 05/23/01 a: b: a: b: a: b: a: b: a: b: a: b: a: b: a: /t f / f ll / / / l / ! 1 / / / t t t /^2-1L ;/ tr rr l/ tt i- , 1 2 , , , , i / / 13 / t i i' t / / r / I titit i iit/t /t t t t till! , , , ,20,21 , , , , ,21 too /f i' i f ii i , , ,19, , i / i' t i i t i , , ,19, , /I i' t r i t t / / t t t 21 21 .9, , t , , / I 6, , , , , .9, f tt t t ,10,11,12,13,14,15, ltttt ,17,18,19,20,21 ,10,11,12,13,14,15,16,17,18,19,20, , , , , , ,15, , 1 7 , 1 8 , 1 9 , 2 0 , 2 1 , , , , ,14,15,16,17,18,19,20, , , , , , ,15,16,17,18,19,20,21 , , , , ,14,15,16,17,18,19,20, ,15, ,15, ,19,20,21 ,19,20, ,15, , 16, ,16, ,19,20, ,19, , ,21 to O -81 - ) DuPont-6515 ) H-24768: Developmental Toxicity Study in Rats ) GROUP III: 100 M G / K G / D A Y ANIMAL NUMBER: OBSERVATION 648578 SACRIFICED BY DESIGN 05/23/01 648581 SACRIFICED BY DESIGN 05/23/01 648593 SACRIFICED BY DESIGN 05/24/01 648594 SACRIFICED BY DESIGN 05/24/01 648595 ALOPECIA BACK ALOPECIA RIGHT HIND QUARTERS ALOPECIA BOTH HIND QUARTERS SACRIFICED BY DESIGN 05/24/01 648599 STAIN CHIN BROWN SALIVATION SACRIFICED BY DESIGN 05/24/01 648603 SACRIFICED BY DESIGN 05/24/01 INDIVIDUAL CLINICAL OBSERVATIONS3 DAYS OF GESTATION ON WHICH SIGN WAS OBSERVED 4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21 ^ , , t t i i i t i i , , i i i i r 21 lilil t , / / ! I / , , , ,21 S. I I I I I I ! ! ! ! ! I ! , , , ,2 1 ^a trilli r i i i r i i i i i /**9-1* a: ! Il II ! , ,14,15, , , , , , b: , 1 3 ,14,15, , , , , , a : , ,14,15,16,17, , , , b: ,13,14,15,16,17, // a : ,18 1 9 , 2 0 , 2 1 b: I f I I I I I I a ,18 19,20, , ,21 a: b: ,14, a : ,19,20, , ,a : // ,21 a ,21 DuPont-6515 Company Sanitized. D oes not contain TSCA CBl -82- s H-24768: Developmental Toxicity Study in Rats G ROUP III: 100 M G / K G / D A Y ANIMAL NUMBER: OBSERVATION 648604 ALOPECIA BOTH FRONT PAW ALOPECIA RIGHT FRONT PAW SACRIFICED BY DESIGN 05/24/01 INDIVIDUAL CLINICAL OBSERVATIONS3 DAYS OF GESTATION ON WHICH SIGN WAS OBSERVED 4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21 a : , ,6,7, , , 1 0 , 1 1 , 1 2 , 1 3 , 1 4 , 1 5 , 1 6 1 7 , 1 8 , 1 9 , 2 0 , 2 1 b: , ,6,7, , , 1 0 , 1 1 , 1 2 , 1 3 , 1 4 , 1 5 , 1 6 1 7 , 1 8 , 1 9 , 2 0 , a : , , , ,8,9, b: , , , ,8,9, a: tt!! 21 ) DuPont-6515 Xuedutod -83- H-24768: Developmental Toxicity Study in Rats G R O U P IV: 400 M G / K G / D A Y ANIMAL NUMBER : OBSERVATION 1# Kt -n" 3 S3 Cfi o > a tp 648523 SALIVATION SACRIFICED BY DESIGN 05/21/01 648525 ALOPECIA BACK ALOPECIA BOTH HIND QUARTERS ALOPECIA LEFT SIDE ALOPECIA BOTH SIDE ALOPECIA ABDOMINAL ALOPECIA PERINEUM SACRIFICED BY DESIGN 05/21/01 648526 ALOPECIA CHEST ALOPECIA ABDOMINAL ALOPECIA RIGHT SIDE ALOPECIA BOTH HIND QUARTERS ALOPECIA BOTH SIDE ALOPECIA RIGHT FRONT LEG ALOPECIA UNDERBODY INDIVIDUAL CLINICAL OBSERVATIONS3 DAYS OF GESTATION ON WHICH SIGN WAS OBSERVED 4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21 a : ,13, a : ,21 a : ,11,12,13,14,15,16,17,18, b: , 1 1 , 1 2 , 1 3 , 1 4 , 1 5 , 1 6 , 1 7 , 1 8 , a : , 1 4 , 1 5 , 1 6 , 1 7 , 1 8 , 1 9 , 20,21 b: , 1 4 , 1 5 , 1 6 , 1 7 , 1 8 , 1 9 , 2 0 , a: b: ,14, a : , 1 5 , 1 6 , 1 7 , 1 8 , 1 9 , 20,21 b: , 1 5 , 1 6 , 1 7 , 1 8 , 1 9 , 2 0 , a : , , 1 6 , 1 7 , 1 8 , 1 9 , 20,21 b: , 1 5 , 1 6 , 1 7 , 1 8 , 1 9 , 2 0 , 2 0a : , , , 1 7 , 1 8 , 1 9 , 20,21 b: , ,16,17,18,19, , a : ,21 ,6,7,8,9,10,11,12,13,14, , , , , , , ,6,7,8,9,10,11,12,13,14, , , , , , , ,6,7,8,9,10,11,12,13,14, , , , , , , ,6,7,8,9,10,11,12,13,14, , , , , , , r / , 0,9,10, , , , , , , , , , , ,,,0,9,10, , ,, , , , , , , , , , ,8,9,10,11,12,13,14,15,16,17,18,19,20,21 , , ,8,9,10,11,12,13,14,15,16,17,18,19,20, , , , , , ,11,12,13,14,15,16,17,18,19,20,21 , , , , , ,11,12,13,14,15,16,17,18,19,20, ,, , , , r, , , , , , , ,14,15,16,17,18, ,, / / t ,14,15,16,17, , ,, , , , , , , , , , ,15,16,17,18,19,20,21 , , , , , , , , , ,15,16,17,18,19,20, -84- DuPont-6515 )) H-24768: Developmental Toxicity Study in Rats GROUP I V : 4 0 0 M G/KG/DAY ANIMAL NUMBER : OBSERVATION INDIVIDUAL CLINICAL OBSERVATIONS3 DA YS OF G E S T A T I O N ON WHICH S I G N WAS O BSER VED 4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21 648526 (C on tin u ed ) A L O P E C I A BOTH FRONT PAW SALIVATION WET PERIN EUM ALOPECIA BACK ALOPECIA NECK A LO PECIA BOTH FRONT LEG SACRIFICED BY DESIGN 0 5 / 2 1 / 0 1 648532 S T A IN PERINEUM YELLOW A L O P E C I A L E F T FRONT PAW DISCHARGE VAGINAL OPENING TAN SACRIFICED BY DESIGN 0 5 / 2 1 / 0 1 648534 S T A IN PERINEUM YELLOW SALIVATION WET NO SE SACRIFICED BY DESIGN 0 5 / 2 1 / 0 1 a: ,15,16,17,18,19,20,21 b: , 1 5 , 1 6 , 1 7 , 1 8 , 1 9 , 2 0 , a : ,15, ,17, ,19, , b: ,15, , , ,19, , 15, , ,18, , , , ,18, , , ,17,18, , , , ,18, , , , , ,19,20,21 , ,18,19,20, , , , , ,21 a : , , , ,8,9, b: , , , ,8,9, a: b: a: a: , I I Il II II ! , Il I II tt , ,15,16,17, ,, , ,15,16,17, ,, ,, , ,17, ,, l ! ,,,,,,, ,21 a: b: , 7 , a: b: a: b: a: ,13, ,15, , ,14, ,16 ,,,, , ,14, , 17, 17, , 19, ,21 ) DuPont-6515 'Company S anitized. D o e s not contain T e ''* r'*l -85 - C om pany Sanitized. D o es not contain TSCA CBI H-24768: Developmental Toxicity Study in Rats G R O U P IV: 400 M G / K G / D A Y ANIMAL NUMBER : OBSERVATION 648539 ALOPECIA ABDOMINAL ALOPECIA BOTH REAR LEG ALOPECIA BOTH HIND QUARTERS ALOPECIA PERINEUM ALOPECIA UNDERBODY ALOPECIA BOTH SIDE ALOPECIA BACK ALOPECIA RIGHT FRONT LEG SACRIFICED BY DESIGN 05/22/01 648540 ALOPECIA ABDOMINAL ALOPECIA RIGHT HIND QUARTERS ALOPECIA BOTH HIND QUARTERS ALOPECIA CHEST ALOPECIA BOTH SIDE SCAB RIGHT SIDE ALOPECIA RIGHT FRONT LEG INDIVIDUAL CLINICAL OBSERVATIONS3 DAYS OF GESTATION ON WHICH SIGN WAS OBSERVED 4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21 ,7,8,9,10,11,12, ,7,8,9,10,11,12, / /8 / ! ! / / , 8, , 9 , 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,21 , 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, , , 10, 11, 12, , , , , , , , , , , 10, 11, 12, , , , , , , , , ,, , 13, 14, 15, 16, 17, 18, 19, 20,21 ,, , 13, 14, 15, 16, 17, 18, 19, 20, ,, , 13, 14, 15, 16, 17, 18, 19, 20,21 ,, , 13, 14, 15, 16, 17, 18, 19, 20, , , , , , 13, 14, 15, 16, 17, 18, 19, 20,21 , , , , , 13, 14, 15, 16, 17, 18, 19, 20, ,, ,, // , , , / 14, 15, 16, , i i , 14, 15, 16, / /t / /tf , , ,, , , ,, !II 2 1/iJ- ,8,9,10,11,12,13,14,15, ,8,9,10,11,12,13,14, , 9, ,9, , 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,21 , 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, / / / , 13, 14, 15, , , , ,, lili 13,14 il il t! , , , , 13, 14, 15, 16, 17, 18, 19, 20,21 , , , , 13, 14, 15, 16, 17, 18, 19, 20, //f ^1--3'/ / / / / / j/ till 13 f i i i i , , , , 13, 14, 15, 16, 17, 18, 19, 20,21 , , , , 13, 14, 15, 16, 17, 18, 19, 20, -86- DuPont-6515 jCpmpany Sanitized. D o es not contain TSCA CBI H-24768: Developmental Toxicity Study in Rats G R O U P IV: 400 M G / K G / D A Y ANIMAL NUMBER: OBSERVATION 648540 (Continued) STAIN PERINEUM YELLOW ALOPECIA UNDERBODY ALOPECIA BACK ALOPECIA BOTH REAR LEG SACRIFICED BY DESIGN 05/22/01 648552 SALIVATION ALOPECIA LEFT HIND QUARTERS STAIN CHIN BROWN ALOPECIA BACK SACRIFICED BY DESIGN 05/22/01 648555 ALOPECIA BOTH HIND QUARTERS ALOPECIA ABDOMINAL ALOPECIA LEFT SIDE ALOPECIA PERINEUM ALOPECIA BOTH SIDE SALIVATION ALOPECIA UNDERBODY INDIVIDUAL CLINICAL OBSERVATIONS3 DAYS OF GESTATION ON WHICH SIGN WAS OBSERVED 4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21 a : , , ,16, , , , , b: , 1 4 , 1 5 , 1 6 , , , , , a : , , ,16,17,18,19,20,21 b: , , 1 5 , 1 6 , 1 7 , 1 8 , 1 9 , 2 0 , a : / i t i 17 t i l t b: I I I 1 6 , 1 7 i i i i a : , , , ,17,18,19,20,21 b: , , , 1 6 , 1 7 , 1 8 , 1 9 , 2 0 , a: a : ,12, ,14, ,16, , , , , a : , ,13,14,15,16,17,18,19,20,21 b: , , 1 3 , 1 4 , 1 5 , 1 6 , 1 7 , 1 8 , 1 9 , 2 0 , a: I l b: a : ,20,21 b: a: I I I ,20, , ,21 ,a : 10 1 1 , 1 2 , 1 3 , 1 4 , 1 5 , 1 6 , 1 7 , 1 8 , 1 9 , 2 0 , 2 1 ,b: 10 1 1 , 1 2 , 1 3 , 1 4 , 1 5 , 1 6 , 1 7 , 1 8 , 1 9 , 2 0 , a: , ,13,14,15, ,,,,, b: I ,A1J3,J.1'*4, / / / / / f a: / ,13, , , , , , ,, b: / i t i t i t t i t a: I *43/44,15, ,,,,, I !b: 1 3--------- ' / 1--" 4-- / / / / / // a : , , ,14,15,16,17,18,19,20,21 b: , , , 1 4 , 1 5 , 1 6 , 1 7 , 1 8 , 1 9 , 2 0 , a : , , ,14,15,16, , , , , a : , , , , ,16,17,18,19,20,21 b: , , , , 1 5 , 1 6 , 1 7 , 1 8 , 1 9 , 2 0 , -87- DuPont-6515 H-24768: Developmental Toxicity Study in Rats ) G R O U P IV: 400 M G / K G / D A Y ANIMAL NUMBER: OBSERVATION 648555 (Continued) ALOPECIA BACK SACRIFICED BY DESIGN 05/22/01 648556 DISCHARGE PERINASAL RED SALIVATION SACRIFICED BY DESIGN 05/22/01 648560 ALOPECIA ABDOMINAL ALOPECIA RIGHT HIND QUARTERS ALOPECIA BOTH HIND QUARTERS ALOPECIA BOTH SIDE ALOPECIA UNDERBODY WET PERINEUM ALOPECIA BACK ALOPECIA BOTH REAR LEG ALOPECIA BOTH FRONT LEG SACRIFICED BY DESIGN 05/22/01 INDIVIDUAL CLINICAL OBSERVATIONS3 DAYS OF GESTATION ON WHICH SIGN WAS OBSERVED 4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21 a: b: a: ,21 a ,15, , a , ,16, a ,21 a : ,8,9,10,11,12,13,14,15, , , , , , b: , 8 , 9 , 1 0 , 1 1 , 1 2 , 1 3 , 1 4 , , , , , , , a : ,8,9,10,11, , , , , , , , , , b: , 8 , 9 , 1 0 , 1 1 , , , , , , , , , , a : , ,, , ,12,13,14,15,16,17,18,19,20,21 b: , , , , , 1 2 , 1 3 , 1 4 , 1 5 , 1 6 , 1 7 , 1 8 , 1 9 , 2 0 , a : , ,, , , ,13,14,15,16,17,18,19,20,21 b: ,,, ,13,14,15,16,17,18,19,20, a: ,,,,,,,, ,16,17,18,19,20,21 b: , , , , , , , , 1 5 , 1 6 , 1 7 , 1 8 , 1 9 , 2 0 , a: b: ,15, a : , ,17,18,19,20,21 b: , 1 6 , 1 7 , 1 8 , 1 9 , 2 0 , a : , ,17,18,19,20,21 b: , 1 6 , 1 7 , 1 8 , 1 9 , 2 0 , a : , , , , ,20,21 b: / / / / / 2 0, a: / /f !t / "21-* ) DuPont-6515 C om p an y San itized . D o e s not con tain TSCA OR! -88- Com pany Sanitized. D oes not contain TSCA CB H-24768: Developmental Toxicity Study in Rats G R O U P IV: 400 M G / K G / D A Y ANIMAL NUMBER: OBSERVATION INDIVIDUAL CLINICAL OBSERVATIONS3 DAYS OF GESTATION ON WHICH SIGN WAS OBSERVED 4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21 648561 DISCHARGE VAGINAL OPENING STAIN CAGEBOARD RED RED STAIN PERINEUM RED SACRIFICED BY DESIGN 05/23/01 648563 ALOPECIA ABDOMINAL ALOPECIA LEFT HIND QUARTERS ALOPECIA BOTH HIND QUARTERS ALOPECIA PERINEUM SALIVATION ALOPECIA UNDERBODY ALOPECIA BOTH SIDE STAIN CHIN BROWN ALOPECIA BACK SCAB BACK ALOPECIA BOTH REAR LEG ALOPECIA BOTH FRONT PAW DISCHARGE VAGINAL OPENING BROWN a: a: b: a: b: a: a b a b a b a b a b a b a b a b a b a b a b a b a b ,12, , 12, , 12, // ,12, ,21 , 7, 8, 9, 10, 11, , , , , , , 7, 8, 9, 10, 11, , , , , , , 7' , , , , 7, , , , , ,, , ,, ,,, ,,, , , , , 8 , 9 , 1 0 , 1 1 , 1 2 , 1 3 , 1 4 , 1 5 , 1 6 , 17.18, 19,20,21 , , 8 , 9 , 1 0 , 1 1 , 1 2 , 1 3 , 1 4 , 1 5 , 1 6 , 17.18, 19,20, i , , 9, 10, 11, , ,,, , , , , 9, 10, 11, , ,,, , , , , , 10, , , 13, ,, , ,18, ,20, ,,,, , ,, , , , 16, , , , , , , 1 2 , 1 3 , 1 4 , 1 5 , 1 6 , 17.18, 19.20.21 , , , , , , 1 2 , 1 3 , 1 4 , 1 5 , 1 6 , 17.18, 19.20, , , , , , , 1 2 , 1 3 , 1 4 , 1 5 , 1 6 , 17.18, 19.20.21 , , , , , , 1 2 , 1 3 , 1 4 , 1 5 , 1 6 , 17.18, 19.20, , 14, , ,16, 17.18, 1 9 , 2 0 , 2 1 ,15,16, 17.18, 19,20, , ,16, ,15,16, , , ,17.18, 19,20,21 , ,16, 1 7 . 1 8 , 1 9 , 2 0 , ,,, , ,16, ,,, , ,16, -89- DuPont-6515 &mpany Sanitized, Does not con H-24768: Developmental Toxicity Study in Rats G R O U P IV: 400 M G / K G / D A Y ANIMAL NUMBER : OBSERVATION 648563 (Continued) ALOPECIA RIGHT FRONT LEG SACRIFICED BY DESIGN 05/23/01 648570 ALOPECIA ABDOMINAL ALOPECIA RIGHT HIND QUARTERS ALOPECIA BOTH HIND QUARTERS SCAB LEFT HIND QUARTERS ALOPECIA LEFT SIDE ALOPECIA PERINEUM ALOPECIA BOTH SIDE ALOPECIA CHEST ALOPECIA UNDERBODY SALIVATION SACRIFICED BY DESIGN 05/23/01 648577 SALIVATION SACRIFICED BY DESIGN 05/23/01 INDIVIDUAL CLINICAL OBSERVATIONS3 DAYS OF GESTATION ON WHICH SIGN WAS OBSERVED 4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21 a : ,20,21 b: ,2 0 , a : , ,21 a ,9,10,11,12,13,14,15,16,17,18,19, b ,9,10,11,12,13,14,15,16,17,18,19, a / ^9 / 1 0 w / , , , , , , , , , , b i 9 i 10 ii i ii ii ii t i a , , ,11,12,13,14,15,16,17,18,19,20,21 b , , ,11,12,13,14,15,16,17,18,19,20, a , , , , ,13,14,15,16,17,18, , , b , , , , ,13,14,15,16,17,18, , , a > <r , , , ,15,16,17,18, ,, b , , , . , ,14,15,16,17,18, , , a , /< / / / / ,16,17,18,19, , b ,,,,,, ,15,16,17,18,19, a it ii i ii , , t ,19,20,21 b i i i i t i i i i 49,20, a / // /! /! tI 19 / b 1 9I t f II // II I J-~' I / a // / / t i I i r t / ,20,21 b i i i/ ii it / / /20, a it i / / // /r i/ 20 a It / // /t // / 77 / *2" *14" a: 7 1 3 , 1 4 , , 1 6 , 1 7 , 719, , 19b: 7 7 7 ,16, 7 , , , a: til 21 DuPont-6515 ) H-24768: Developmental Toxicity Study in Rats ) G R O U P IV: 400 M G / K G / D A Y ANIMAL NUMBER: OBSERVATION 648579 SALIVATION WET CHIN STAIN CHIN BROWN SACRIFICED BYDESIGN 05/23/01 648583 ALOPECIA ABDOMINAL ALOPECIA BOTH HIND QUARTERS SALIVATION ALOPECIA BOTH SIDE WET PERINEUM ALOPECIA PERINEUM ALOPECIA BACK ALOPECIA UNDERBODY STAIN PERINASAL BROWN SACRIFICED BY DESIGN 05/24/01 INDIVIDUAL CLINICAL OBSERVATIONS3 DAYS OF GESTATION ON WHICH SIGN WAS OBSERVED 4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21 a: b: a: a: b: a: a: b: a: b: a: b: a: b: a: b: a: b: a: b: a: b: a: b: a: / / ,1 1 1 t 3 - 3 f, !1/ f /1 2 f iti , ,1 1 f 1 ,14, , f1/ t itti i / / /1 1 !t ,15, 1ll t i t i l i ,17, / , i 1i iti III III 11 !/ // // , ,21 ,8,9,10,11,12,13,14,15, , , , , , ,8,9,10,11,12,13,14, , , , , , , ,8,9,10,11,12,13,14,15,16,17,18,19,20,21 ,8,9,10,11,12,13,14,15,16,17,18,19,20, ,1 0 , 2 0' / / t ! I I I I / / ,11,12,13,14,15,16,17,18,19,20,21 ,11,12,13,14,15,16,17,18,19,20, ,1 2 , ' / 14~ 15 ///// ,13,14,,,,,,, ,15,16,17,18,19,20,21 ,14,15,16,17,18,19,20, ,16,17,18,19,20,21 15 15 17 18 19 20 / / , ,20, / / , , ,21 ) DuPont-6515 C om pany Sanitized. D oes not contain TSCA CB! -91 - H-24768: Developmental Toxicity Study in Rats G R O U P IV: 4 00 M G / K G / D A Y ANIMAL NUMBER: OBSERVATION 648584 ALOPECIA RIGHT HIND QUARTERS ALOPECIA BOTH HIND QUARTERS ALOPECIA ABDOMINAL ALOPECIA BOTH SIDE ALOPECIA UNDERBODY DIARRHEA ALOPECIA BACK ALOPECIA LEFT REAR LEG SALIVATION ALOPECIA BOTH REAR LEG SACRIFICED BY DESIGN 05/24/01 648586 SACRIFICED BY DESIGN 05/24/01 INDIVIDUAL CLINICAL OBSERVATIONS3 DAYS OF GESTATION ON WHICH SIGN WAS OBSERVED 4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21 a: b: a : ,10,11,12,13,14 ,15,16, 17.18 ,19,20,21 b: , 1 0 , 1 1 , 1 2 , 1 3 , 1 4 ,15,16, 1 7 . 1 8 ,19,20, a : , 1 8, , , , b: #18, , , , a : , 1 0 , 1 1 , 1 2 , 1 3 , 1 4 ,15,16, 1 7 . 1 8 , 19, 20,21 b: , 1 0 , 1 1 , 1 2 , 1 3 , 1 4 ,15,16, 1 7 . 1 8 ,19, 2 0 , a: , , 1 1 , 1 2 , 1 3 , 1 4 , 1 5 , 1 6 , 1 7 . 1 8 ,19, 20,21 b: , , 1 1 , 1 2 , 1 3 , 1 4 ,15,16, 1 7 . 1 8 ,19, 2 0 , a: b: ,12, a : , ,14 ,15,16, 1 7 . 1 8 ,19, 20,21 b: ,13,14 ,15,16, 17.18 ,19, 20, a : , ,16, 17, b: ,15,16, 17, a: , ,16, ,19, b: ,15, , // a : ,18 ,19, 20,21 ,b: , 1 8 ,19, 2 0 , a : 21 a ,21 DuPont-6515 Com pany Sanitized. D oes not contain CAO O > o CJ -92- > H-24768: Developmental Toxicity Study in Rats GROUP IV: 400 MG/KG/DAY ANIMAL NUMBER: OBSERVATION 648589 ALOPECIA CHEST ALOPECIA RIGHT FRONT PAW ALOPECIA BOTH FRONT PAW ALOPECIA ABDOMINAL ALOPECIA LEFT HIND QUARTERS ALOPECIA LEFT REAR LEG SACRIFICED BY DESIGN 05/24/01 648590 STAIN PERINEUM YELLOW STAIN PERINEUM BROWN ALOPECIA LEFT FRONT PAW SALIVATION SACRIFICED BY DESIGN 05/24/01 648597 SALIVATION SACRIFICED BY DESIGN 05/24/01 INDIVIDUAL CLINICAL OBSERVATIONS3 DAYS OF GESTATION ON WHICH SIGN WAS OBSERVED 4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21 a : , 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,21 b: , 1 1 , 1 2 , 1 3 , 1 4 , 1 5 , 1 6 , 1 7 , 1 8 , 1 9 , 2 0 , a: , , 12, 13, , , , , , , , b: ! ! -*- ** ! tI Il t // / a: / , , ,14,15,16, , ,, , b: , , , 1 3 , 1 4 , 1 5 , 1 6 , , , , , a: ,, , , , 15, 16, 17, 18, 19, 20,21 b: ,, , , , 15, 16, 17, 18, 19, 20, a: ,, , , , , , , 18, 19, 20,21 b: , , , , , , , , 1 8 , 1 9 , 2 0 , a: ,, , ,, , , , , ,20,21 b: /f t !t r t ! f ,20, a: a: b: , ,13,14i i t i ,19, , a: , , , ,15,16,17, b: , , , , 1 5 , 1 6 , 1 7 , l i t a: I f I It ti b: / / r IR i/ a: t rt // ,19, a: f t r /f / / ,21 a ,17, ,19, a ,21 ) DuPont-6515 C om pany Sanitized. D o es not contain TSCA CBI -93- H-24768: Developmental Toxicity Study in Rats DuPont-6515 APPENDIX E Gross Postmortem Findings Compony -94- contain T SCA CB t P es n-- H-24768: Developmental Toxicity Study in Rats Gross Postmortem Findings Explanatory Notes Footnotes a Pregnant by stain. Abbreviations = No Data NAD = No Abnormalities Detected DuPont-6515 -95- C om paq T\ot CO' .poes rSCAcB' H-24768: Developmental Toxicity Study in Rats GROSS POSTMORTEM FINDINGS DuPont-6515 Group I : 0 m g/k g/d ay A nim al Number Dam C ode 648517 648520 648522 648528 648535 648536 648544 648549 648553 648554 648559 648566 648567 648571 648573 648576 648582 648587 648588 648592 648601 648602 13 5 11 18 16 21 27 31 24 39 25 48 57 59 58 55 47 72 79 75 74 73 S tru ctu re(s) -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- F in d in g (s) NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD -96- GO' ed $a' T$' con Al H-24768: Developmental Toxicity Study in Rats GROSS POSTMORTEM FINDINGS DuPont-6515 Group II: 50 mg/kg/day A nim al Number Dam C od e 648518 648524 648529 648531 648537 648538 648541 648542 648546 648547 648551 648562 648564 648565 648574 648575 648580 648585 648591 648596 648598 648600 1 14 22 9 4 15 30 29 26 36 43 52 53 65 64 50 60 85 69 87 84 68 S tru ctu re(s) -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- F in d in g (s) NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD -97- p 55 co mp ^ sa""'Md H-24768: Developmental Toxicity Study in Rats DuPont-6515 GROSS POSTMORTEM FINDINGS Group III: 100 mg/kg/day A nim al Number Dam C ode 648519 648521 648527 648530 648533 648543 648545 648548 648550 648557 648558 648568 648569 648572 648578 648581 648593 648594 648595 648599 648603 648604 20 12 3 17 7 44 38 35 23 40 28 63 62 61 45 46 86 83 82 78 71 88 S tru ctu re(s) -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- F in d in g (s ) NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD -98- m 2: KiO' c' *ts<* H-24768: Developmental Toxicity Study in Rats GROSS POSTMORTEM FINDINGS DuPont-6515 G rou p IV : 4 0 0 m g /k g /d a y A n im al N um ber Dam C od e 648523 648525 648526 648532 648534 648539 648540 648552 648555 648556 648560 6485619 648563 648570 648577 648579 648583 648584 648586 648589 648590 648597 6 19 10 2 8 42 33 41 34 32 37 56 51 49 54 66 77 80 76 67 70 81 S tru ctu re(s) -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- F in d in q (s) NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD m- 9 9 - 0*p TS( n ojico1 Oos H-24768: Developmental Toxicity Study in Rats DuPont-6515 APPENDIX F Individual Reproductive Data - 100- ornpm not contain TSCAc B l H-24768: Developmental Toxicity Study in Rats Individual Reproductive Data Explanatory Notes Footnotes a Pregnant by stain. Abbreviations - - - = No Data DuPont-6515 -101- Company5 annteed.Poftfin9lcontail1 TSCACBI ) H-24768: Developmental Toxicity Study in Rats ) ) DuPont-6515 INDIVIDUAL REPRODUCTIVE DATA3 GROUP I : 0 MG/KG/DAY ANIMAL NUMBER CORPORA LUTEA NIDATIONS RESORPTIONS TOTAL EARLY LATE DEAD FETUSES LIVE FETUSES TOTAL FEMALE MALE MEAN FETAL W E I G H T (G) 6 4 8 5 1 7 14 12 1 1 648 5 2 0 18 17 -- -- -- 6 4 8 5 2 2 14 13 -- -- -- 6 4 8 5 2 8 17 14 -- -- -- 648 5 3 5 14 14 -- ---- 6 4 8 5 3 6 14 13 -- -- -- -- -- -- -- -- 6 4 8 5 4 4 14 14 -- -- -- -- 6 4 8 5 4 9 15 14 -- -- ---- 6 4 8553 15 14 -- -- -- -- 648554 19 18 -- -- -- -- 6 4 8 5 5 9 15 15 1-- 1-- 648566 17 16 -- -- -- -- 648567 21 14 -- -- -- -- 6485 7 1 15 12 -- -- -- -- 6 4 8 5 7 3 15 13 -- -- -- -- 648 5 7 6 15 14 1 1 -- -- 6 4 8 5 8 2 14 14 1 1 -- -- 648587 15 14 -- -- -- -- 648588 18 16 5 5 -- -- 6 4 8 5 9 2 15 14 -- -- -- -- 6 4 8 6 0 1 14 14 -- -- -- -- 648602 21 16 -- -- -- -- O oo 3 3 (ofi >o 2 11 10 1 17 6 11 13 7 6 14 8 6 14 7 7 13 8 5 14 8 6 14 7 7 14 7 7 18 10 8 14 6 8 16 10 6 14 7 7 12 5 7 13 6 7 13 5 8 13 4 9 14 10 4 11 5 6 14 9 5 14 4 10 16 10 6 5.73 5.40 5.36 5.71 5.74 5.38 5.50 5.31 5.72 5.32 5.22 4.78 5.88 5.85 5.58 5.54 5.15 5.76 5.96 5.36 5.43 5.38 (Company Sanitized. D oes - 102- ) H-24768 : Developmental Toxicity Study in Rats ) oo 3 "O a 3 K O 3 N a ao 9 3 O O O 3 3 HCO O > O S G R O U P II: 50 M G / K G / D A Y ANIMAL NUMBER CORPORA LUTEA NIDA TIONS 6 4 8 5 1 8 12 10 648524 17 17 6 4 8 5 2 9 15 14 6 4 8 5 3 1 13 11 648537 19 17 6 4 8 5 3 8 14 14 648541 15 15 648542 22 18 648546 11 11 6 4 8 5 4 7 16 16 6 4 8 5 5 1 16 15 648562 15 11 6 4 8 5 6 4 16 16 648 5 6 5 14 12 6 4 8 5 7 4 14 14 6 4 8 5 7 5 15 15 6 4 8 5 8 0 13 12 648 5 8 5 19 17 6 4 8 5 9 1 15 14 6 4 8 5 9 6 15 13 6485 9 8 15 14 6 4 8 6 0 0 12 12 INDIVIDUAL REPRODUCTIVE DATA3 RESORPTIONS TOTAL EARLY LATE -- ____ ____ -- -- ____ -- -- ______ -- -- ______ -- -- ____ 1 1 ____ 1 1 ____ -- -- ____ -- -- ____ -- -- ____ -- -- ______ -- ---- 1 -- 1 -- -- ______ -- -- ______ ------ 1 -- 1 -- -- -- ------ ------ -- -- ______ DEAD FETUSES LIVE FETUSES TOTAL FEMALE MALE MEAN FETAL W E I G H T (G) ____ -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- 10 17 14 11 17 14 14 17 11 16 15 11 16 11 14 15 12 16 14 13 14 12 64 5 12 4 10 56 98 86 59 7 10 47 5 11 69 83 97 74 77 96 66 4 12 68 67 86 84 5.78 5.79 5.82 5.47 5.11 5.54 4.92 5.36 5.62 5.59 5.19 5.71 5.52 5.41 5.92 5.15 5.83 5.37 5.21 5.57 5.38 5.54 - 103 - H-24768: Developmental Toxicity Study in Rats DuPont-6515 GROUP III : 100 M G / K G/DAY ANIMAL NUMBER CORPORA LUTEA NIDATIONS 6 4 8 5 1 9 13 12 648521 17 16 6 4 8 5 2 7 11 10 6 4 8 5 3 0 13 13 648533 19 15 648543 16 16 648545 14 14 648548 15 15 6 4 8 5 5 0 19 18 6 4 8 5 5 7 16 15 6 4 8 5 5 8 16 14 6 4 8 5 6 8 16 13 6 4 8 5 6 9 15 13 648572 19 15 6 4 8 5 7 8 18 12 6 4 8 5 8 1 16 16 648593 21 16 648594 18 18 648595 11 11 6 4 8 5 9 9 17 13 6 4 8 6 0 3 13 12 6 4 8 6 0 4 13 12 INDIVIDUAL REPRODUCTIVE DATA3 RESORPTIONS TOTAL EARLY LATE _- ____ ____ -- ____ ____ -- ____ ____ -- ____ ____ -- 2 2-- ____ ____ -- 1 1-- 1 1-- ____ __ _ -- 8 ____ 8 ____ _ _ -- ____ _ _ _ -- 1 1-- ____ ___ -- 1 ____ 1 1 1-- -- ____ -- -- ____ -- -- ____ -- -- ____ -- -- ____ -- DEAD FETUSES LIVE FETUSES TOTAL FEMALE MALE MEAN FETAL W E I G H T (G) 12 7 5 5.96 -- 16 7 9 5.17 -- 10 5 5 5.23 -- 13 9 4 5.76 -- 15 6 9 5.04 -- 14 10 4 5.19 -- 14 9 5 5.59 -- 14 3 11 5.94 -- 17 8 9 5.18 -- 15 5 10 4.78 -- 6 51 4.43 -- 13 4 9 5 .74 -- 13 5 8 5.84 -- 14 3 11 5.61 -- 12 5 7 5.70 -- 15 6 9 5.02 -- 15 6 9 5.56 -- 18 9 9 5.26 -- 11 4 7 5.59 -- 13 4 9 5.18 -- 12 8 4 5.52 -- 12 2 10 5.59 Company Sanitized. D oes not contain TSCA CB ) H-24768: Developmental Toxicity Study in Rats ) ) DuPont-6515 G R O U P IV: 400 M G / K G / D A Y ANIMAL NUMBER CORPORA LUTEA NIDATIONS 648523 648525 648526 648532 648534 648539 648540 648552 648555 648556 648560 6485613 648563 648570 648577 648579 648583 648584 648586 648589 648590 648597 17 17 24 16 16 16 16 22 15 13 16 -- 15 15 17 23 12 16 14 15 16 14 17 16 17 14 15 14 13 15 13 13 13 ______ 15 14 17 14 11 14 14 15 14 12 INDIVIDUAL REPRODUCTIVE DATA3 RESORPTIONS TOTAL EARLY LATE -- 1 -- -- -- -- 4 ____ ____ -- ______ 3 1 3 -- 1 -- 1 -- -- -- ____ 1 -- ____ ____ ____ 3 ____ ____ -- ____ 3 1 2 ______ 1 ____ 1 ______ ______ ____ ___ -- -- -- -- -- -- 1 -- -- -- ___ -- 1 -- -- -- -- -- -- -- DEAD FETUSES LIVE FETUSES TOTAL FEMALE MALE MEAN FETAL W E I G H T (G) _____ -- -- -- -- -- -- -- -- -- -- ___ -- -- -- -- -- -- -- -- -- 17 16 16 14 15 14 13 11 13 13 13 12 13 14 14 10 14 13 15 14 12 10 7 79 88 95 96 59 85 56 67 76 76 48 67 86 77 19 68 3 10 78 95 66 4.54 4.88 4.34 4.16 4.90 4.41 4.58 5.00 4.98 4.61 4.90 4.53 4.77 4.78 5.08 4.66 4.70 5.52 4.85 4.90 4.91 Company Sanitized. D oes not contain TSCA CBi - 105- H-24768: Developmental Toxicity Study in Rats DuPont-6515 APPENDIX G Individual Fetal Weights and Alterations it co n ta in T SC ft CM - 106- Pom panit Santtteed. D oes n H-24768: Developmental Toxicity Study in Rats Individual Fetal Weights and Alterations DuPont-6515 Explanatory Notes For ease o f recording, many of the findings have been abbreviated or coded, as listed below: ar bil cen It Iu NAD rt th -- = arch(es) = bilateral = centrum or centra = left = lumbar = No Abnormalities Detected = right = thoracic = No Data * Subcutaneous hemorrhage that was not present in utero. Renal papillary sizes refer to papillary development using the scheme o f Woo and Hoar.(3) Alterations are classed as: N = Notes DV = Developmental Variations VR = Variation due to Retarded Development M = Malformations Numbers are used to: Indicate renal papillary size Identify specific stemebra Refer to skeletal position for ribs or vertebra Specify skull bones according to the following key: 1. Interparietal 2. Parietal 3. Frontal 4. Nasal 5. Premaxilla 6. Maxilla 7. Zygoma 8. Squamosal 9. Tympanic annulus 10. Basioccipital 11. Exoccipital 12. Supreoccipital 13. Hyoid - 107Q om pany San itized . D o e s not contain TSCA CBS H-24768: Developmental Toxicity Study in Rats Individual Fetal Weights and Alterations DuPont-6515 Explanatory Notes (Continued) Due to technical errors that occurred during the skeletal processing step, the following list of fetuses were damaged during the evisceration process and the listed bones were unavailable for examination: Group I: 0 mg/kg/day Dam 648553 Fetus 13 Rib - 121t Group IT. 50 mg/kg/day Dam 648600 Fetus 7 Rib - 81t Group III: 100 mg/kg/day Dam 648599 Dam 648599 Dam 648599 Dam 648519 Dam 648594 Fetus 7 Fetus 7 Fetus 9 Fetus 3 Fetus 3 Humerus It Carpals bil Carpals rt Rib - 121t Stemebra - 4,6 Group IV: 400 mg/kg/day Dam 648539 Dam 648539 Dam 648523 Dam 648540 Dam 648552 Dam 648570 Dam 648577 Fetus 5 Fetus 5 Fetus 15 Fetus 7 Fetus 4 Fetus 12 Fetus 13 Carpal bil Scapula rt Rib - 121t Rib - 9, lOrt Rib - th 4, 5rt Stemebra - 6 Rib - th 8rt Due to technical errors that occurred during the skeletal processing step, the following skeletal specimens were disarticulated and thus, were unavailable for examination: Group I Dam No. 648553 Fetuses No. 5, 6, and 11 Group II Dam No. 648537 Fetuses 1-17 Group m Dam No. 648599 Fetus 8 Group IV Dam No. 648539 Fetuses 6-9 and 11-14 -108 - Company ganitzf; ,,ot contain T S C A C B I . H-24768: Developmental Toxicity Study in Rats DuPont-6515 I N D I V I D U A L FETAL WEIGHTS (grams) A N D A L T E R ATIONS G R O U P I: 0 M G / K G / D A Y DAM NO./ F E T U S NO. FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 648517 1 2 3 4 5 6 7 8 9 10 11 5.39 5.66 5.87 5.72 5.80 5.57 6.28 5.89 5.41 5.86 5.60 Skull Vertebra Kidney Skull Skull Vertebra Skull Vertebra NAD R e t a r d e d O s s i f i c a t i o n (6bil) Retarded Ossification (cen thlO) NAD NAD S m a l l P a p i l l a - S i z e 2 (rt) Retarded Ossification ( 1 , 1 2 ; 2 , 6 , 7bil) NAD Retarded Ossification (1,12 ;2 , 6 , b i l ) Retarded Ossification (cen thll) NAD R e t a r d e d O s s i f i c a t i o n (6bil) Retarded Ossification (cen thll) VR VR VR VR VR VR VR VR 648520 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 5.35 5.51 5.21 5.48 5.58 4.99 5.28 5.60 5.32 4.92 5.64 5.42 5.93 5.12 5.47 5.32 Vertebra Sternebra NAD NAD Retarded Ossification (cen thl3) NAD NAD NAD NAD NAD NAD NAD M i s a l i g n e d (1,3) NAD NAD NAD NAD NAD VR DV -109- pgm panx Sanitized. D oes not contain TSCA1 H-24768: Developmental Toxicity Study in Rats DuPont-6515 INDIVIDUAL FETAL WEIGHTS (grams) A ND ALTERATIONS GROUP I: 0 MG/KG/DAY DAM NO./ FETUS NO. FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 648520 (Cont.) 17 5.67 648522 1 2 3 4 5 6 7 8 9 5.65 5.32 5.66 5.44 5.50 4.98 5.32 5.63 5.03 10 5.22 11 5.36 12 5.09 13 5.44 648528 1 5.47 2 6.12 3 5.77 4 6.14 5 5.95 6 5.52 7 5.64 8 5.41 9 5.90 10 5.63 11 5.99 12 5.29 13 5 . 4 0 14 5.70 Kidney Rib Vertebra Vertebra Rib Vertebra Vertebra P a pilla - Size 3 (right) NAD NAD Supernumerary (short 13bil) NAD NAD NAD NAD NAD Retarded Ossification (cen thl2) NAD NAD NAD NAD Retarded Ossification (cen thl2) NAD NAD NAD NAD NAD NAD NAD S u p e rnumerary (site 141t) NAD NAD NAD Retarded Ossification (cen thl3) Retarded Ossification (cen t h l O ,13) VR DV VR VR DV VR VR Com pany Sanitized. D o es not contain TSCA CB! H-24768: Developmental Toxicity Study in Rats_____________________________________________ DuPont-6515 I NDIVIDUAL FETAL WEIGHTS (grams) A N D A L T E R A T I O N S G R O U P I: 0 M G / K G / D A Y DAM NO./ FETUS NO. FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 48535 1 2 3 4 5 6 7 8 9 10 11 12 13 14 648536 1 2 3 4 5 6 7 8 9 10 11 12 13 5.88 6.08 6.04 5.98 5.34 5.83 5.63 6.14 5.47 5.53 5.88 5.59 5.19 5.73 5.73 5.62 5.27 5.32 5.06 5.33 5.14 5.57 5.31 5.15 5.28 5.41 5.72 Skull Kidney Mandible Skull Mandible Skull Vertebra Mandible Skull Mandible Skull NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD Retarded Ossification (6bil;7,Bit) P a p i l l a - S i z e 3 (bil) R e t a r d e d O s s i f i c a t i o n (bil) Retarded Ossification (2,6 b i l ) NAD R e t a r d e d O s s i f i c a t i o n (bil) Retarded Ossification (6,7,8bil) Retarded Ossification (cen thll) NAD NAD R e t a r d e d O s s i f i c a t i o n (bil) Retarded Ossification (1,12 ;2 , 6 , 7 , B b i l ) NAD R e t a r d e d O s s i f i c a t i o n (bil) Retarded Ossification (7,8 1 t ;6 b i l ) NAD VR VR VR VR VR VR VR VR VR VR VR D oes not contain TSCA TM Pom pany Sanitized. - Ill - H-24768: Developmental Toxicity Study in Rats_____________________________________________ DuPont-6515 I NDIVIDUAL FETAL WEIGHTS (grams) A N D A L T E R A T I O N S G R O U P I: 0 M G / K G / D A Y DAM NO./ FETUS NO. FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 648544 1 2 3 4 5 5 7 8 9 10 11 12 13 14 5.58 6.11 5.52 5.83 5.50 5.50 5.32 5.09 4.91 5.61 5.34 5.26 5.48 5.96 Vertebra Vertebra Rib Vertebra Skull Vertebra Kidney Vertebra Skull Vertebra Vertebra Rib Vertebra Vertebra Vertebra NAD Retarded Ossification (cen thll) Retarded Ossification (cen thll) Supernumerary (site 14bil) Retarded Ossification (cen th8) R e t a r d e d O s s i f i c a t i o n (6bil) Retarded Ossification (cen thl2) P a p i l l a - S i z e 3 (bil) Retarded Ossification (cen thll) R e t a r d e d O s s i f i c a t i o n (6bil) Retarded Ossification (cen t h l l ,12) NAD Retarded Ossification (cen t h l O ,12) S u p e r numerary (site 141t) Retarded Ossification (cen thl2) NAD Retarded Ossification (cen thll) Retarded Ossification (cen thll) VR VR DV VR VR VR VR VR VR VR VR DV VR VR VR 648549 1 2 3 4 5 6 4.93 5.70 5.22 5.54 5.38 4.86 NAD NAD NAD NAD NAD NAD Company Sanitized. Does not contain TSCA C . -112- H-24768: Developmental Toxicity Study in Rats DuPont-6515 INDIVIDUAL FETAL WEIGHTS (grams) A N D A L T ERATIONS GROUP I: 0 MG/KG/DAY DAM NO./ FETUS NO. FETUS WT . STRUCTURE FINDING(S) CLASSIFICATION 6 4 8 5 4 9 (Cont .) 7 5.10 8 5.59 9 5.37 10 4.88 11 5.51 12 5.50 13 5.3 6 14 5.42 Vertebra Vertebra Retarded Ossification (cen thl2) NAD NAD NAD NAD NAD NAD Retarded Ossification (cen thl2) VR VR 648553 1 2 3 4 5 6 7 8 9 10 11 12 13 14 5.79 6.44 5.84 6.04 5.50 5.21 5.74 5.89 5.68 5.71 5.52 5.96 5.48 5.32 Rib Rib Kidney Kidney Skull NAD Supernumerary (site 14rt) NAD S u p e r n u m e r a r y (site 14 rt) NAD NAD NAD NAD NAD NAD P a p i l l a - S i z e 3 (bil) NAD S m a l l P a p i l l a - S i z e 2 (It) R e t a r d e d O s s i f i c a t i o n (2 bil) DV DV VR VR VR 648554 1 2 3 4 5 6 7 8 5.69 5.78 5.81 5.64 5.31 5.65 5.56 4.67 Skull Skull Skull NAD NAD NAD Retarded Ossification NAD Retarded Ossification ( 6 , 7 , 8bil) NAD Retarded Ossification (2,6bil) (2bil) VR VR VR Company Sanlfeed. Does not contain TSCACB1 - 113- H-24768: Developmental Toxicity Study in Rats DuPont-6515 INDIVIDUAL FETAL WEIGHTS (grams) A N D ALTER A T I O N S GROUP I: 0 MG/KG/DAY DAM NO./ F E T U S NO. FETUS WT . S T R U C T U R E FINDING(S) CLASSIFICATION 6 4 8 5 5 4 (Cont .) 9 5.71 10 4.62 11 4.42 12 5.02 13 5.35 14 4.96 15 5.55 16 5.01 17 4.75 18 6.21 Vertebra Retarded Ossification (cen thl0-12) NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD VR 648559 1 2 3 4 5 6 7 8 9 10 11 12 13 14 5.66 5.49 5.23 5.57 5.59 5.54 4.76 5.09 5.48 5.60 5.07 5.17 3.36 5.44 Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra Retarded Ossification (cen thll-13) Retarded Ossification (cen thl2) NAD Retarded Ossification (cen t h 6 , 11) Retarded Ossification (cen thll) Retarded Ossification (cen thll) NAD NAD NAD NAD Retarded Ossification (cen thll) NAD NAD Retarded Ossification (cen t h l O , 11) VR VR VR VR VR VR VR ^O ntpany San itized . D o e s not contain TSCA CBI - 114- H-24768: Developmental Toxicity Study in Rats DuPont-6515 INDIVIDUAL FETAL WEIGHTS (grams) A ND ALTERATIONS GROUP I : 0 MG/KG/DAY DAM NO./ FE T U S NO. FETUS WT . STRUC T U R E FINDING(S) CLASSIFICATION 648566 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 4.78 5.16 4.74 4.89 4.54 5.00 4.50 4.69 5.19 4.82 4.28 4.96 4.81 4.61 4.59 4.95 Vertebra Vertebra Sternebra Retarded Ossification (cen thll) NAD NAD NAD NAD NAD NAD Retarded Ossification (cen thll) NAD NAD Retarded Ossification NAD NAD NAD NAD NAD (6) VR VR VR 648567 1 2 3 4 5 6 7 8 9 10 11 12 13 14 5.80 5.92 5.85 6.08 5.70 5.89 6.00 5.62 6.06 5.87 6.10 5.74 5.86 5.77 Kidney Kidney Small NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD Small NAD Papilla Papilla - Size 2 - Size 2 (bil) (bil) VR VR 648571 1 2 5.30 6.23 NAD NAD - 115 - S an itized . D o e s not co n tain TSCA CBI Company H-24768: Developmental Toxicity Study in Rats DuPont-6515 INDIVIDUAL FETAL WEIGHTS (grams) A N D ALTERATIONS GROUP I : 0 MG/KG/DAY DAM NO./ FETUS NO. FETUS WT . STRUCTURE FINDING(S) CLASSIFICATION 648571 3 4 5 6 (Cont .) 5.83 5.75 5.68 5.76 7 6.00 8 6.38 9 5.84 10 6.12 11 5.79 12 5.47 Kidney Skull P a p i l l a - S i z e 3 (It) NAD NAD Retarded Ossification (2b i l ;6r t ) NAD NAD NAD NAD NAD NAD VR VR 648573 1 2 3 4 5 6 7 8 9 10 11 12 13 5.41 5.63 5.58 5.92 5.73 4.77 5.76 5.36 5.73 5.77 5.87 5.47 5.54 Vertebra Kidney Rib NAD Retarded Ossification (cen thl2) NAD NAD NAD NAD P a p i l l a - S i z e 3 (rt) NAD NAD NAD NAD Supernumerary (site 14rt) NAD VR VR DV 648576 1 2 3 4 5 6 7 5.52 5.82 5.50 5.83 4.63 5.87 5.27 Kidney Rib Skull Vertebra NAD NAD P a p i l l a - S i z e 3 (bil) S u p e r n u m e r a r y (site 141t) Retarded Ossification {611 ) Retarded Ossification (cen thll) NAD NAD VR DV VR VR Com pany Sanitized. D oes not contain TSCA CBt -116- H-24768: Developmental Toxicity Study in Rats DuPont-6515 INDIVIDUAL FETAL WEIGHTS (grams) A N D ALTERATIONS GROUP I: 0 MG/KG/DAY DAM NO./ FETUS NO. FETUS W T . STRUCTURE FINDING(S) CLASSIFICATION 6 4 8 5 7 6 (Cont.) 8 5.34 9 10 11 12 13 648582 1 2 3 4 5 6 7 8 9 10 11 12 13 648587 1 2 3 4 5 6 7 5.62 5.45 5.85 5.85 5.44 4.92 5.20 4.73 5.17 5.01 5.54 5.75 5.02 4.97 5.09 5.28 5.18 5.12 6.20 5.49 6.07 5.67 5.73 5.66 5.50 Skull Vertebra Vertebra Vertebra Vertebra Vertebra Rib Vertebra Kidney Kidney Rib R e t a r d e d O s s i f i c a t i o n (6rt) Retarded Ossification (cen th!2) Retarded Ossification (cen thl2) Retarded Ossification (cen thll) Retarded Ossification (cen thll) Retarded Ossification (cen thll) Supernumerary (site14bil) VR VR VR VR VR VR DV NAD Retarded Ossification (cen t h l l , 12) NAD NAD NAD NAD NAD NAD NAD NAD Papi l l a - S i z e 3 (bil) NAD Small Papilla - Size 2 (bil) VR VR VR NAD NAD NAD NAD Supernumerary NAD NAD (site 14bil) DV .Company S an itized . D o e s not contain TSCA CBI -117- H-24768: Developmental Toxicity Study in Rats DuPont-6515 INDIVIDUAL FETAL WEIGHTS (grams) A N D ALTERATIONS GROUP I: 0 MG/KG/DAY DAM NO./ FETUS NO. FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 648587 (Cont.) 8 5.43 9 5.54 10 5.43 11 5.86 12 5.96 13 5.91 14 6.17 648588 1 2 3 4 5 6 7 8 9 10 11 5.47 5.68 6.64 6.09 6.22 5.85 6.35 5.60 6.13 5.69 5.79 648592 1 2 3 4 5 6 7 5.44 5.48 5.49 5.73 5.42 5.35 5.39 8 5.28 9 5.17 10 5.21 11 4. 9 7 Vertebra Kidney Rib Vertebra Kidney Kidney Kidney Kidney Skull Vertebra Skull Retarded Ossification (cen thll-13) P a p i l l a - S i z e 3 (rt) NAD S u p e r n u m e r a r y (site 14lt) Retarded Ossification (cen thl2) NAD NAD VR VR DV VR Small Papilla - Size 2 NAD Small Papilla - Size 2 NAD P a p i l l a - S i z e 3 (It) NAD P a p i l l a - S i z e 3 (It) NAD NAD NAD NAD (bil) (bil) VR VR VR VR NAD NAD NAD NAD NAD Retarded Ossification Retarded Ossification (cen th9,11,12) Retarded Ossification NAD NAD NAD (6bil) (2,6bil) VR VR VR not contain TSCACBI (Company Sanitized. D oes -118- H-24768: Developmental Toxicity Study in Rats DuPont-6515 INDIVIDUAL FETAL WEIGHTS (grams) A N D ALTERATIONS GROUP I : 0 MG/KG/DAY DAM NO./ FETUS NO . FETUS WT . STRUCTURE F I N D I N G (S) CLASSIFICATION 6 4 8 5 9 2 (C o n t .) 12 5.54 13 5.2 7 14 5 . 3 1 Vertebra Retarded Ossification (cen thll) NAD NAD VR 648601 1 2 3 4 5 6 7 8 9 10 11 12 13 14 5.42 5.60 5.48 5.84 5.05 5.42 5.69 5.47 5.52 5.05 5.26 5.52 5.22 5.47 Kidney Kidney Skull Skull Sternebra NAD NAD S m a l l P a p i l l a - S i z e 2 (bil) NAD NAD NAD NAD NAD P a p i l l a - S i z e 3 (It) Retarded Ossification ( 6 b i l ;12) NAD R e t a r d e d O s s i f i c a t i o n (6bil) M i s a l i g n e d (4) NAD VR VR VR VR DV 648602 1 2 3 4 5 6 7 8 9 10 5.07 5.24 5.62 5.24 5.19 5.55 5.54 5.48 5.19 5.83 Skull Vertebra Skull Vertebra Skull NAD Retarded Ossification NAD Retarded Ossification (cen thll) NAD Retarded Ossification Retarded Ossification (cen thl2) NAD NAD NAD Retarded Ossification (2bil) (61t) (2bil) VR VR VR VR VR Com pany Sanitized. D oes not contain TSCA CBI - 119- H-24768: Developmental Toxicity Study in Rats DuPont-6515 INDIVIDUAL FETAL WEIGHTS (grams) A ND A L T E R A T I O N S GROUP I: 0 MG/KG/DAY DAM NO./ FETUS NO. FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 648602 (Cont.) 11 5.28 12 4.99 13 5.34 14 5.77 15 5.30 16 5.45 Vertebra Retarded Ossification (cen t h l l ,12) NAD NAD NAD NAD NAD NAD VR C om pany S a n itized . D o e s not con tain TSCA CBI - 120- H-24768: Developmental Toxicity Study in Rats DuPont-6515 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP II: 50 MG/KG/DAY DAM NO./ F E T U S NO. FETUS W T . STRUC T U R E FINDING(S) CLASSIFICATION 648518 1 2 3 4 5 6 7 8 9 10 648524 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 5.56 5.65 5.66 6.06 5.71 5.97 6.03 5.63 5.38 6.13 Vertebra Anus Tail 5.72 5.99 6.01 6.00 5.99 5.88 5.39 6.47 5.42 6.03 5.92 5.91 5.54 4.69 5.67 5.89 5.83 Kidney Kidney Retarded Ossification (cen thlO) NAD Imperforate Filamentous (with hemorrhagic tissue) NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD Small Papilla - Size 2 NAD NAD NAD NAD NAD NAD NAD P a p i l l a - S i z e 3 (bil) NAD NAD (It) VR M M VR VR 648529 1 2 3 4 5.86 5.78 5.95 5.98 NAD NAD NAD NAD Company Sanitized. Does not contain TSCA CBI H-24768: Developmental Toxicity Study in Rats DuPont-6515 INDIVIDUAL FETAL WEIGHTS (grams) A N D A L T E R A T I O N S G R O U P II: 50 M G / K G / D A Y DAM NO./ FETUS NO. FETUS W T . STRUCTURE FINDING(S) CLASSIFICATION 648529 5 6 7 8 9 10 11 12 13 14 (Cont .) 5.37 6.10 5.92 5.73 5.91 5.90 5.80 5.75 5.76 5.66 648531 1 2 5.70 5.71 3 4 5 6 7 8 9 10 11 648537 1 2 3 4 5 6 7 8 9 10 5.58 5.57 5.15 5.31 5.34 5.62 5.71 5.59 4.85 5.10 5.13 5.17 5.49 5.21 4.59 5.08 5.11 4.85 5.44 Skull Vertebra Vertebra Skull Rib NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD R e t a r d e d O s s i f i c a t i o n (2 bil) Retarded Ossification (cen thll) NAD Retarded Ossification (cen thl2) NAD R e t a r d e d O s s i f i c a t i o n (2 bil) NAD NAD S u p e r n u m e r a r y (short 1 3 1 t) NAD NAD VR VR VR VR DV NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD , a Does not contain TSCAc company Sanitized- - 122- H-24768: Developmental Toxicity Study in Rats DuPont-6515 INDIVIDUAL FETAL WEIGHTS (grams) A N D ALTERATIONS GROUP II: 50 MG/KG/DAY DAM NO./ FETUS NO. FETUS W T . STRUCTURE FINDING(S) CLASSIFICATION 648537 11 12 13 14 15 16 17 (Cont.) 4.86 5.13 5.38 5.04 5.25 5.04 4.92 648538 1 2 5.67 5.88 3 4 5 6 7 8 9 10 11 12 13 14 648541 1 2 3 4 5 6 7 8 9 10 6.00 5.62 5.77 5.62 5.55 5.86 4.98 4.58 5.29 5.30 5.75 5.75 4.74 4.77 4.85 4.85 5.25 5.24 5.20 5.14 5.40 4.81 Skull Vertebra Kidney Skull Skull Sternebra Kidney NAD NAD NAD NAD NAD NAD NAD NAD R e t a r d e d O s s i f i c a t i o n (2bil) Retarded Ossification (cen t h l l ,12) NAD NAD S m a l l P a p i l l a - S i z e 2 (It) NAD NAD R e t a r d e d O s s i f i c a t i o n (6bil) NAD R e t a r d e d O s s i f i c a t i o n (2bil) R e t a r d e d O s s i f i c a t i o n (6) NAD NAD NAD NAD VR VR VR VR VR VR P a p i l l a - S i z e 3 (bil) NAD NAD NAD NAD NAD NAD NAD NAD NAD VR not con tain TSCA CBI C om pany Sanitized. D o es - 123- H-24768: Developmental Toxicity Study in Rats DuPont-6515 INDIVIDUAL FETAL WEIGHTS (grams) A N D A L T ERATIONS GROUP II: 50 MG/KG/DAY DAM NO./ FETUS NO. FETUS W T . STRUC T U R E FINDING(S) CLASSIFICATION 648541 11 12 13 14 (Cont .) 4.99 4.92 4.74 3.92 NAD NAD NAD NAD 648542 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 5.37 5.55 5.65 5.31 5.51 5.54 4.62 5.35 5.44 4.96 5.08 5.55 5.50 5.37 5.06 5.39 5.90 Kidney Kidney Vertebra Kidney NAD NAD NAD NAD NAD NAD NAD NAD Small Papilla - Size 2 NAD NAD NAD NAD NAD Small Papilla - Size 1 Retarded Ossification (cen t h l O , 11) P a p i l l a - S i z e 3 (bil) (bil) (bil) VR VR VR VR 648546 1 2 3 4 5 6 7 8 9 10 5.46 6.03 6.04 5.70 5.54 5.24 5.40 5.68 5.95 5.10 Kidney Kidney Vertebra NAD NAD P a p i l l a - S i z e 3 (bil) NAD Small Papilla - Size 2 Retarded Ossification (cen thl2) NAD NAD NAD NAD NAD (bil) VR VR VR Company Sanitized. D oes not contain TSCA CBI -124- H-24768: Developmental Toxicity Study in Rats DuPont-6515 INDIVIDUAL F E T A L WEIGHTS (grams) A N D A L T E R A T I O N S G R O U P II: 50 M G / K G / D A Y DAM NO./ F E T U S NO. F E T U S W T S T R U C T U R E _____________________ F I N D I N G (S)______________ C L A S S I F I C A T I O N 648546 (Cont.) 11 5.71 648547 1 2 3 5.47 5.69 5.62 4 5.73 5 5.88 6 5.68 7 5.56 8 5.62 9 5.80 10 5.65 11 5.59 12 5.86 13 5.48 14 4.90 15 5.54 16 5.35 Kidney Vertebra Vertebra Kidney Vertebra Kidney Rib Rib Kidney Rib Vertebra 648551 1 2 3 4 5 6 7 8 9 10 11 12 13 5.22 5.19 5.11 5.64 5.02 5.21 5.29 5.53 5.42 5.40 4.74 4.77 5.45 Kidney Skull P a p i l l a - S i z e 3 (bil) VR NAD NAD Retarded Ossification (cen thl2) Retarded Ossification (cen t h l l , 12) P a p i l l a - S i z e 3 (It) Retarded Ossification (cen t h l 2 , 13) S m a l l P a p i l l a - S i z e 1 (It) NAD Supernumerary (site 14bil) NAD Supernumerary (site 141t) NAD S m a l l P a p i l l a - S i z e 2 (bil) NAD Supernumerary (site 14lt) Retarded Ossification (cen thll) VR VR VR VR VR DV DV VR DV VR NAD NAD NAD NAD NAD NAD NAD NAD P a p i l l a - S i z e 3 (rt) Retarded Ossification NAD NAD NAD (7 bil) VR VR om pany Sanitized. nDnoeeBs nnoot contain TSCA CB! - 125- H-24768: Developmental Toxicity Study in Rats DuPont-6515 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP II: 50 MG/KG/DAY DAM NO./ FETUS NO. FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 6 4 8 5 5 1 (Cont.) 14 5.10 15 4.76 Vertebra 648562 1 2 3 4 5 6 7 8 9 10 11 5.55 5.78 6.27 5.69 5.53 5.61 5.77 5.73 5.41 5.60 5.91 Kidney Skull Skull Vertebra Kidney Vertebra 648564 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 5.79 4.88 5.45 5.40 5.68 5.53 5.98 5.38 5.65 5.99 5.43 5.87 5.25 5.34 5.39 5.38 Skull Kidney NAD Retarded Ossification (cen thll) VR P a p i l l a - S i z e 3 (rt) NAD NAD R e t a r d e d O s s i f i c a t i o n (2bil) NAD Retarded Ossification (2bil) NAD NAD Retarded Ossification (cen thl2) NAD P a p i l l a - S i z e 3 (bil) Retarded Ossification (cen thll) VR VR VR VR VR VR NAD R e t a r d e d O s s i f i c a t i o n (2 bil) S m a l l P a p i l l a - S i z e 2 (It) NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD VR VR C om pany Sanitized. D oes not contain TSCA CBI - 126- H-24768: Developmental Toxicity Study in Rats DuPont-6515 INDIVIDUAL FETAL WEIGHTS (grams) A N D ALTERATIONS G R O U P XI: 50 M G / K G / D A Y DAM NO./ FETUS NO. FETUS W T . STRUCTURE FINDING(S) CLASSIFICATION 648565 1 2 3 4 5 6 7 8 9 10 11 648574 1 2 3 4 5 6 7 8 9 10 11 12 13 14 648575 1 2 5.62 5.02 5.88 5.37 5.19 5.47 5.72 5.68 5.29 5.26 5.03 Vertebra Skull Skull 6.20 5.65 6.48 5.71 6.39 5.84 5.25 6.24 5.99 6.50 5.74 5.70 4.59 6.56 Kidney Vertebra 5.04 5.35 Vertebra Vertebra Retarded Ossification (cen thll) NAD NAD NAD NAD Retarded Ossification NAD NAD NAD Retarded Ossification (21t;6bil) NAD (6bil) VR VR VR NAD NAD NAD NAD Small Papilla - Size 2 NAD NAD Retarded Ossification (cen t h l l , 12) NAD NAD NAD NAD NAD NAD (bil) VR VR Retarded Ossification (cen thlO) Retarded Ossification (cen t h l l - 13) VR VR con tain TSCA O5* Com pany S a n t t t e e d . D oes not --' -127- H-24768: Developmental Toxicity Study in Rats DuPont-6515 INDIVIDUAL FETAL WEIGHTS (grams) A N D ALTERATIONS G R O U P II: 50 M G / K G / D A Y DAM NO./ FETUS NO. FETUS W T . STRUCTURE FINDING(S) CLASSIFICATION 6 4 8 5 7 5 (Cont .) 3 4.69 4 4.83 5 5.18 6 4.93 7 5.36 8 5.33 9 5.31 10 5.28 11 5.42 12 5.29 13 5.23 14 5.12 15 4. 9 5 Vertebra Vertebra Vertebra Vertebra Vertebra Vertebra Skull Vertebra Vertebra Vertebra Rib Vertebra Vertebra Vertebra Retarded Ossification (cen t h l O ,12) Retarded Ossification (cen thlO-12) Retarded Ossification (cen thll-13) Retarded Ossification (cen th9-13) Retarded Ossification (cen thlO-12) Retarded Ossification (cen thl2) NAD R e t a r d e d O s s i f i c a t i o n (2bil) Retarded Ossification (cen thlO-13) Retarded Ossification (cen th8,12) Retarded Ossification (cen th8,12) Supernumerary (site 14rt) Retarded Ossification (cen thll) Retarded Ossification (cen t h l O , 11) Retarded Ossification (cen t h l O , 11) VR VR VR VR VR VR VR VR VR VR DV VR VR VR 648580 1 2 3 4 5 6 7 6.19 6.46 6.11 5.01 5.53 5.54 5.96 Rib Kidney NAD Supernumerary NAD NAD NAD NAD Small Papilla (site 14bil) - S i z e 2 (rt) DV VR n 0 t contain f S C A C ------------- ;-- -128- Qnnltteed' D o 8 C o m p a n y -------------- H-24768: Developmental Toxicity Study in Rats DuPont-6515 INDIVIDUAL FETAL WEIGHTS (grams) A N D ALTERATIONS GROUP II: 50 MG/KG/DAY DAM NO./ F E T U S !NO. F E T U S W T . S T R U C T U R E FINDING(S) CLASSIFICATION 6 4 8 5 8 0 (Cont .) 8 5.87 9 5.70 10 6.10 11 5.54 12 5.93 Vertebra Rib Kidney Retarded Ossification (cen thll) NAD Supernumerary (site 14rt) P a p i l l a - S i z e 3 (bil) NAD VR DV VR 648585 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 5.54 5.45 5.31 5.60 5.40 5.44 5.34 5.34 5.70 5.49 5.39 5.03 5.47 5.09 5.07 5.18 Skull Kidney Skull Kidney Vertebra NAD NAD NAD Retarded Ossification ( 2 r t ;6 , 7bil) P a p i l l a - S i z e 3 (rt) Retarded Ossification P a p i l l a - S i z e 3 (It) NAD NAD NAD NAD NAD NAD Retarded Ossification (cen t h l 2 ,13) NAD NAD (61t ) VR VR VR VR VR 648591 1 2 3 4 5 6 7 8 9 10 5.45 4.94 4.86 5.59 5.26 5.41 5.42 5.16 5.01 5.33 Rib Rib Kidney Supernumerary NAD NAD Supernumerary NAD NAD NAD NAD Small Papilla NAD (site 14bil) (site 14bil) - S i z e 2 (bil) DV DV VR . - A nnes nol contain TSCA CB ------------- Cowpattf.Sgnized- p-------------------------- - 129 - ^ ---------........... H-24768: Developmental Toxicity Study in Rats DuPont-6515 INDIVIDUAL FETAL WEIGHTS (grams) A N D ALTERATIONS G R O U P II: 50 M G / K G / D A Y DAM NO./ FETUS NO. FETUS W T . STRUCTURE FINDING(S) CLASSIFICATION 648591 11 12 13 14 (Cont. ) 5.10 5.23 5.10 5.08 Vertebra NAD NAD NAD Retarded Ossification (cen thll) VR 648596 1 2 3 4 5 6 7 8 9 10 11 12 13 5 . 84 5.76 5.50 5.22 5.53 5.65 5.77 5.50 5.31 6 . 08 5.61 5.38 5.20 Kidney Vertebra Vertebra Vertebra Kidney Vertebra Kidney Vertebra Vertebra Vertebra Kidney Vertebra Vertebra Small Papilla - Size 2 Retarded Ossification (cen thll-13) Retarded Ossification (cen thll) Retarded Ossification (cen t h l l , 13) NAD P a p i l l a - S i z e 3 (bil) Retarded Ossification (cen thl3) P a p i l l a - S i z e 3 (bil) Retarded Ossification (cen thl2) Retarded Ossification (cen t h l l , 12) Retarded Ossification (cen t h l l , 12) P a p i l l a - S i z e 3 (bil) Retarded Ossification (cen thll) Retarded Ossification (cen thl2) NAD (bil) VR VR VR VR VR VR VR VR VR VR VR VR VR 648598 1 2 3 5.28 5.52 5 . 77 Kidney NAD NAD S m a l l P a p i l l a - S i z e 2 (bil) VR - 130- nol contain TSCA < C o m p a qQSfalnnit_ized* 0 s H-24768: Developmental Toxicity Study in Rats DuPont-6515 INDIVIDUAL FETAL WEIGHTS (grams) A N D ALTERATIONS GROUP II: 50 MG/KG/DAY DAM NO./ FETUS NO. FETUS W T . STRUCTURE FINDING(S) CLASSIFICATION 6 4B598 (Cont.; 4 5.70 5 5.85 6 5.15 7 5.21 8 4.70 9 5.21 10 5.34 11 5.60 12 5.45 13 5.08 14 5.47 Vertebra Vertebra Skull Vertebra Vertebra Vertebra Vertebra Nares Vertebra Kidney Vertebra 18600 1 2 3 4 5 6 7 8 9 10 11 12 5.45 5.48 5.65 6.02 5.27 5.48 5.02 5.51 5.20 5.72 5.70 5.98 Rib Kidney Rib Retarded Ossification (cen t h l l , 12) NAD Retarded Ossification (cen thlO) R e t a r d e d O s s i f i c a t i o n (6bil) Retarded Ossification (cen thl2) Retarded Ossification (cen thl2) Retarded Ossification (cen thl2) Retarded Ossification (cen thll) NAD Malformation (naris atresia, bil) Retarded Ossification (cen t h l l , 12) NAD P a p i l l a - S i z e 3 (bil) Retarded Ossification (cen thll) VR VR VR VR VR VR VR M VR VR VR NAD NAD NAD NAD NAD NAD NAD NAD NAD Supernumerary Small Papilla Supernumerary (site 1 4 It) - S i z e 2 (bil) (site 14bil) DV VR DV Company Sanitized. Does not contain TSCA CBI - 131 - H-24768: Developmental Toxicity Study in Rats DuPont-6515 INDIVIDUAL FETAL WEIGHTS (grams) A N D ALT E R A T I O N S GROUP I I I : 100 MG/KG/DAY DAM NO./ F E T U S NO. FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 648519 1 2 3 4 5 6 7 8 9 10 11 12 5.84 6.11 5.82 5.60 6.22 6.07 6.10 5.71 5.81 5.78 6.36 6.10 Skull Vertebra Kidney Vertebra NAD R e t a r d e d O s s i f i c a t i o n (2 bil) Retarded Ossification (cen thll) P a p i l l a - S i z e 3 (bil) Retarded Ossification (cen thlO) NAD NAD NAD NAD NAD NAD NAD NAD VR VR VR VR 648521 1 2 3 4 5 6 7 8 9 10 11 12 13 14 5.51 5.29 5.51 5.82 5.86 5.10 5.19 4.90 5.16 4.56 5.33 5.47 4.60 4.68 Vertebra Vertebra Kidney Vertebra Vertebra Vertebra Rib NAD NAD Retarded Ossification (cen t h l l , 12) Retarded Ossification (cen thlO) NAD NAD P a p i l l a - S i z e 3 (It) Retarded Ossification (cen thlO) NAD Retarded Ossification (cen th3,ll) NAD Retarded Ossification (cen thl0-12) NAD NAD Supernumerary (short 13bil) VR VR VR VR VR VR DV C om pany San itized . D o e s not con tain TSCA CBv - 132- H-24768: Developmental Toxicity Study in Rats DuPont-6515 INDIVIDUAL FETAL WEIGHTS (grams) A N D A L T E R ATIONS G R O U P III: 100 M G / K G / D A Y DAM NO./ FE T U S NO. FETUS W T . S T R U C T U R E FINDING(S) CLASSIFICATION 6 4 8 5 2 1 ( C o n t .) 15 4.47 16 5.34 648527 1 2 3 4 5 6 7 8 9 10 5.32 5.44 5.12 5.18 5.24 5.34 4.81 5.58 4.92 5.35 Skull Rib Skull Kidney Skull Vertebra 648530 1 2 3 4 5 6 7 8 9 10 11 12 13 648533 1 2 3 4 5.46 6.15 5.93 5.75 5.79 5.82 5.65 5.55 5.77 5.62 5.66 5.34 6.45 Rib Kidney Rib 5.50 5.60 5.29 4.89 Vertebra R e tarded O s s i f ication (2bil) Supernumerary (short 13rt) NAD VR DV NAD NAD NAD NAD NAD R e t a r d e d O s s i f i c a t i o n (61t) P a p i l l a - S i z e 3 (bil) R e t a r d e d O s s i f i c a t i o n (6bil) NAD Retarded Ossification (cen thl2) VR VR VR VR NAD S u p e r n u m e r a r y (site 141t) NAD NAD P a p i l l a - S i z e 3 (rt) NAD NAD NAD NAD NAD NAD NAD S u p e r n u m e r a r y (site 14rt) DV VR DV NAD Retarded Ossification (cen thl2) NAD NAD VR not contain TSCAC Company Sanitized. D oes -133- H-24768: Developmental Toxicity Study in Rats_____________________________________________ DuPont-6515 INDIVIDUAL FETAL WEIGHTS (grams) A N D A L T E R ATIONS G R O U P III: 100 M G/KG/DAY DAM NO./ FET U S NO. FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 648533 5 6 (Cont.) 4.26 5.18 7 5.10 8 4.98 9 5.17 10 5.36 11 4.81 12 5.25 13 4.85 14 4.62 15 4.72 648543 1 2 3 4 5 6 7 8 9 10 11 12 13 14 4.89 5.31 4.95 5.52 4.89 4.61 4.97 5.44 5.63 5.71 5.09 5.30 4.90 5.40 Vertebra Kidney Kidney Kidney Skull Skull Vertebra 648545 1 2 5.41 6.06 Heart &/or Greater Vessels Heart &/or Greater Vessels Kidney NAD Retarded Ossification (cen thl2) NAD NAD NAD NAD NAD NAD NAD NAD NAD VR Sm a l l P a p i l l a - S i z e 2 (bil) NAD NAD NAD S m a l l P a p i l l a - S i z e 2 (bil) NAD NAD NAD Sm a l l P a p i l l a - S i z e 2 (bil) NAD NAD R e t a r d e d O s s i f i c a t i o n (2 bil) NAD R e t a r d e d O s s i f i c a t i o n (2 bil) Retarded Ossification (cen thll-12) VR VR VR VR VR VR Malformation (double outlet It vent) Septal Defect (interventricular) Sm a l l P a p i l l a - S i z e 2 (bil) NAD M M VR -134- C om pany S an itized . D o e s not con tain TSCA < H-24768: Developmental Toxicity Study in Rats DuPont-6515 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP III: 100 MG/KG/DAY DAM NO./ FETUS NO. FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 648545 3 4 5 6 7 8 9 10 11 12 13 14 (Cont.) 5.61 5.73 5.61 5.91 5.71 5.66 5.22 5.31 5.95 5.54 5.52 5.06 648548 1 2 5.53 6.15 3 5.91 4 6.31 5 6.06 6 5.84 7 6.40 8 5.75 9 5.73 10 5.61 11 5.74 12 6.39 13 5.83 14 5.84 Kidney Kidney Rib Vertebra Vertebra Vertebra Vertebra Kidney Vertebra Vertebra S m a l l P a p i l l a - S i z e 2 (bil) NAD P a p i l l a - S i z e 3 (bil) NAD NAD NAD NAD Supernumerary (site 14rt) NAD NAD NAD NAD VR VR DV NAD Retarded Ossification (cen thlO) NAD NAD Retarded Ossification (cen t h l O , 12) Retarded Ossification (cen thlO) NAD Retarded Ossification (cen t h l O , 11) NAD NAD P a p i l l a - S i z e 3 (bil) Retarded Ossification (cen thl3) Retarded Ossification (cen thlo-12) NAD NAD VR VR VR VR VR VR VR Company Sanitized. Does not contain TSCA CE H-24768: Developmental Toxicity Study in Rats DuPont-6515 INDIVIDUAL F ETAL WEIGHTS (grams) A N D A L T E R A T I O N S GROUP III: 100 MG/KG/DAY DAM NO./ F E T U S NO. F E T U S WT. S T R U C T U R E _____________________ F I N D I N G (S)______________ C L A S S I F I C A T I O N S48550 1 2 3 4 5 S 7 8 9 10 11 12 13 14 15 16 17 648557 1 2 3 4 5 6 7 8 9 10 11 12 13 14 5.39 5.44 5.49 5.25 5.06 5.39 5.42 5.65 5.40 4.95 5.57 4.72 4.90 4.95 4.51 4.93 5.09 Rib Rib Vertebra 5.39 4.52 4.87 5.35 4.33 4.75 4.91 5.00 4.46 4.34 4.85 5.04 4.85 4.82 Skull KidneyRib Rib Skull Rib Skull Supernumerary (site 14bil) NAD NAD NAD NAD NAD NAD NAD S u p e r n u m e r a r y (site 1 4 It) NAD Retarded Ossification (cen thll) NAD NAD NAD NAD NAD NAD DV DV VR NAD R e t a r d e d O s s i f i c a t i o n (2 bil) NAD NAD P a p i l l a - S i z e 3 (It) S u p e r n u m e r a r y (site 13 bil) S u p e r n u m e r a r y (site 13 rt) R e t a r d e d O s s i f i c a t i o n (2 bil) NAD NAD NAD Supernumerary (site I3bil) R e t a r d e d O s s i f i c a t i o n (2 bil) NAD NAD NAD NAD VR VR DV DV VR DV VR Gprnpany Sanitized. Does not contain TSCA c o t H-24768: Developmental Toxicity Study in Rats DuPont-6515 INDIVIDUAL FETAL WEIGHTS (grams) A N D A L T ERATIONS GROUP III: 100 MG/KG/DAY DAM NO./ FETUS NO. FETUS W T . STRUCTURE FINDING(S) CLASSIFICATION 648557 (Cont.) 15 4.17 648558 1 2 3 4 5 6 648568 1 3.75 4.45 4.10 4.65 4.91 4.74 5.59 2 3 4 5 6 7 8 9 10 11 12 13 648569 1 2 3 4 6.32 5.54 5.88 6.35 5.66 5.83 5.07 5.43 5.85 5.81 5.37 5.90 5.96 5.86 5.60 5.90 Kidney Rib Vertebra Skull Kidney Rib Vertebra Skull Kidney Vertebra Kidney Skull Kidney Rib S m a l l P a p i l l a - S i z e 1 (bil) Super n u m e r a r y (site I3lt) VR DV NAD NAD Retarded Ossification (cen t h l l - 1 3 ) NAD NAD Retarded Ossification (2bil) VR VR S m a l l P a p i l l a - S i z e 2 (bil) S u p e rnumerary (site 14lt) Retarded Ossification (cen t h l O , 13) R e t a r d e d O s s i f i c a t i o n (6bil) P a p i l l a - S i z e 3 (It) Retarded Ossification (cen thl2) S m a l l P a p i l l a - S i z e 2 (bil) NAD NAD R e t a r d e d O s s i f i c a t i o n (61t) NAD NAD NAD NAD S m a l l P a p i l l a - S i z e 1 (rt) VR DV VR VR VR VR VR VR VR NAD NAD NAD Supernumerary (site 141t) DV Company Sanitized. Does not contain TSCA n 31 H-24768: Developmental Toxicity Study in Rats DuPont-6515 INDIVIDUAL FETAL WEIGHTS (grams) A N D ALTERATIONS GROUP III: 100 MG/KG/DAY DAM NO./ FETUS NO . FETUS WT . STRUCTURE FINDING(S) CLASSIFICATION 6485S9 (Cont.) 5 5.96 6 5.49 7 5.99 8 5.37 9 6.59 10 5.82 11 5.81 12 5.54 13 6.04 Vertebra Kidney Kidney Skull Kidney Rib Retarded Ossification (cen thll) P a p i l l a - S i z e 3 (bil) NAD P a p i l l a - S i z e 3 (rt) R e t a r d e d O s s i f i c a t i o n (2bil) P a p i l l a - S i z e 3 (bil) Supernumerary (site 14bil) NAD NAD NAD VR VR VR VR VR DV 648572 1 2 3 4 5 6 7 8 9 10 11 12 13 14 5.58 5.90 5.68 5.84 5.74 5.77 5.86 5.23 5.29 5.70 5.37 5.67 5.62 5.26 Vertebra Kidney Rib Kidney Skull Kidney NAD Retarded Ossification (cen thll) Small Papilla - Size 2 ( r t ; s i z e 3 It) NAD NAD NAD S u p e r n u m e r a r y (site 13 bil) NAD P a p i l l a - S i z e 3 (It) R e t a r d e d O s s i f i c a t i o n (2 bil) NAD NAD S m a l l P a p i l l a - S i z e 2 (It) NAD VR VR DV VR VR VR 648578 1 2 3 4 5 6 6.21 6.00 5.07 5.48 5.84 5.64 Kidney Kidney Small Papilla - Size 2 NAD P a p i l l a - S i z e 3 (It) NAD NAD NAD (bil) VR VR Company Sanitized. D o es not contain TSCA CBI - 138- H-24768: Developmental Toxicity Study in Rats DuPont-6515 INDIVIDUAL FETAL WEIGHTS (grams) AN D ALTER A T I O N S GROUP III: 100 MG/KG/DAY DAM NO./ FETUS NO. FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 64 8 5 7 8 (Cont.) 7 6.22 8 5.42 9 5.82 10 5.48 11 5.78 12 5.46 KidneyKidney Small Papilla - Size 2 (lt;size 3 rt) NAD P a p i l l a - S i z e 3 (It) NAD NAD NAD VR VR 648581 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 648593 1 2 3 4 2.09 4.96 5.47 5.65 5.39 5.31 5.46 4.36 5.47 5.79 5.14 5.03 4.92 5.12 5.20 Spleen Sternebra Vertebra Vertebra Skull Vertebra Vertebra Skull Kidney 5.56 5.21 5.92 5.87 Skull Pale M i s a l i g n e d (1) Retarded Ossification (cen th5) NAD NAD NAD NAD Retarded Ossification (cen thll) NAD R e t a r d e d O s s i f i c a t i o n (2bil) Retarded Ossification (cen thlO) NAD Retarded Ossification (cen th.7,12) NAD R e t a r d e d O s s i f i c a t i o n (2bil) NAD NAD S m a l l P a p i l l a - S i z e 2 (bil) N DV VR VR VR VR VR VR VR NAD NAD NAD Retarded Ossification (2 bil) VR C om pany S a n itized . D o e s not c e r ta in TSCA CB! - 139- H-24768: Developmental Toxicity Study in Rats_____________________________________________ DuPont-6515 I NDIVIDUAL FETAL WEIGHTS (grams) A N D ALT E R A T I O N S GROUP III: 100 MG/K G / D A Y DAM NO./ FETUS NO. FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 648593 (Cont.) 5 5.61 6 5.47 7 5.31 8 5.78 9 5.76 10 5.21 11 5.84 12 5.40 13 5. 7 1 14 5.48 15 5.23 Vertebra Skull Skull Vertebra Vertebra Retarded Ossification (cen t h l 2 ) NAD NAD NAD Retarded Ossification NAD Retarded Ossification NAD Retarded Ossification (cen thll) NAD NAD Retarded Ossification (cen thll-12) (2 bil) (2 bil) VR VR VR VR VR 648594 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 648595 1 6.05 5.23 3.87 5.06 5.29 5.10 5.32 4.93 4.94 5.45 5.67 5.72 5.33 5.61 5.16 5.36 5.23 5.40 Kidney 5.52 NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD Small NAD Papilla - Size 2 (bil) VR NAD C o m p a n y Sanitized. D o e s not contain TSCA C B I - 140- H-24768: Developmental Toxicity Study in Rats DuPont-6515 INDIVIDUAL FETAL WEIGHTS (grams) A ND ALTERATIONS GROUP III: 100 MG/KG/DAY DAM NO./ FETUS NO. FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 648595 2 3 4 5 6 7 8 9 10 11 ( C o n t .) 5.71 5.42 5.51 5.15 5.38 5.41 6.15 5.88 5.72 5.68 648599 1 2 3 4 5 6 7 8 9 10 11 12 13 5.45 5.58 5.27 5.56 4.23 5.21 4.93 5.10 5.49 5.06 4.95 5.14 5.38 648603 1 5.29 2 5.29 3 5.60 4 5.27 5 4.96 6 5.43 7 5.59 Rib Rib Skull Skull Kidney Kidney Rib Rib Rib Rib Vertebra Vertebra Supernumerary (site 13lt) Supernumerary (short 13rt) R e t a r d e d O s s i f i c a t i o n (2bil) NAD NAD NAD NAD NAD R e t a r d e d O s s i f i c a t i o n (6bil) S m a l l P a p i l l a - S i z e 2 (bil) DV DV VR VR VR NAD NAD P a p i l l a - S i z e 3 (rt) NAD NAD NAD Supernumerary (site 14bil) NAD NAD NAD Supernumerary (site 14bil) Supernumerary (site 14rt) Supernumerary (site 14rt) VR DV DV DV DV Retarded Ossification (cen thll) NAD Retarded Ossification (cen thl0-12) NAD NAD NAD NAD VR VR not contain TSCA CBi Company Sanitized. D oes - 141 - H-24768: Developmental Toxicity Study in Rats DuPont-6515 INDIVIDUAL FETAL WEIGHTS (grams) AND A L T ERATIONS GROUP III: 100 MG/KG/DAY DAM NO./ FETUS NO. FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 6 4 8 6 0 3 (C o n t .) B 5.21 9 5.76 10 5.88 11 6.35 12 5.63 Vertebra Vertebra Vertebra 648604 1 2 3 4 5 6 7 8 9 10 11 12 5.87 5.66 5.71 6.08 5.52 5.65 5.83 5.15 5.24 5.70 5.17 5.48 Vertebra Vertebra Vertebra Retarded Ossification (cen t h l l , 12) NAD NAD Retarded Ossification (cen t h l l , 12) Retarded Ossification (cen thll-13) Retarded Ossification (cen thll) NAD NAD Retarded Ossification (cen thlO) NAD Retarded Ossification (cen thll) NAD NAD NAD NAD NAD NAD VR VR VR VR VR VR Company Sanitized. D o e s not contain TSCA CBI - 142- H-24768: Developmental Toxicity Study in Rats DuPont-6515 INDIVIDUAL FETAL WEIGHTS (grams) A N D ALTERATIONS GROUP IV: 400 MG/KG/DAY DAM NO./ FETUS NO. FETUS WT . STRUCTURE F I N D I N G (S) CLASSIFICATION 648523 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 4.56 4.19 4.75 4.49 4.67 3.92 4.20 5.03 5.04 4.77 4.68 4.46 4.44 4.48 3.85 4.84 4.74 Skull Vertebra Skull Skull NAD NAD NAD Retarded Ossification Retarded Ossification (cen t h l l ,12) NAD NAD NAD NAD NAD NAD NAD NAD Retarded Ossification NAD Retarded Ossification NAD (2bil) (2bil) (1) VR VR VR VR 648525 1 2 3 4 5 6 7 8 9 10 5.30 5.10 5.27 4.77 4.25 3.74 4.40 5.24 5.35 5.12 Skull Skull Vertebra Rib Vertebra Rib Skull Subcutis Skull Vertebra Skull NAD Retarded Ossification (2,3 b i l ) NAD R e t a r d e d O s s i f i c a t i o n (2bil) Retarded Ossification (cen t h l l , 12) Supernumerary (short 141t) Retarded Ossification (cen thl2) Supernumerary (site 14lt) Retarded Ossification (2,3 b i l ) H emorrhage (head*) Retarded Ossification (2bil) Retarded Ossification (cen t h l l , 12) R e t a r d e d O s s i f i c a t i o n (2bil) VR VR VR DV VR DV VR N VR VR VR Com pany Sanitized. D oes no. contain TSCA CBi - 143- H-24768: Developmental Toxicity Study in Rats DuPont-6515 INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP IV: 400 MG/KG/DAY DAM NO./ FETUS NO. FETUS WT . STRUCTURE FINDING(S) CLASSIFICATION 648525 (Cont.) 11 5.08 12 5. 2 9 13 4.8 8 14 4.82 15 4.97 16 4.44 Vertebra Skull Rib Skull Vertebra Vertebra Skull Vertebra Retarded Ossification (cen thl2) Retarded Ossification (2bil) Supernumerary (site 14bil) Retarded Ossification (1,12;2bil) Retarded Ossification (cen thlO-13) Retarded Ossification (cen t h l O ,11,13) R e t a r d e d O s s i f i c a t i o n (2bil) Retarded Ossification (cen t h l l , 12) VR VR DV VR VR VR VR VR 648526 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 3.94 4.49 4.40 4.16 4.37 4.46 4.12 4.39 4.69 4.36 4.20 4.31 4.49 4.35 4.06 4.66 Subcutis Vertebra Skull Rib Skull Sternebra Sternebra Kidney Sternebra Sternebra H e m o r r h a g e (c h i n * ) Retarded Ossification (cen t h l 2 ) Retarded Ossification (2bil) S u p e r n u m e r a r y (short 1 3 It) Retarded Ossification (2bil) R e t a r d e d O s s i f i c a t i o n (6) NAD R e t a r d e d O s s i f i c a t i o n (6) NAD Papilla - Size 3 (left ) NAD NAD R e t a r d e d O s s i f i c a t i o n (6) NAD NAD R e t a r d e d O s s i f i c a t i o n (6) NAD N VR VR DV VR VR VR VR VR VR 648532 1 2 3 4.62 4.16 4.35 NAD NAD NAD Com pany Sanitized. D oes not contain r e r o n i - 144- H-24768: Developmental Toxicity Study in Rats DuPont-6515 I NDIVIDUAL FETAL WEIGHTS (grams) A N D A L T E R A T I O N S G R O U P IV: 4 0 0 M G / K G / D A Y DAM NO./ F E T U S NO. FETUS W T . S T R U C T U R E F I N D I N G (S) CLASSIFICATION 648532 4 5 6 7 8 9 10 11 12 13 14 (Cont.) 4.31 4.27 3.56 4.21 4.08 4.09 3.89 4.09 4.28 4.42 3.91 Skull Rib Skull Skull Rib Skull R e t a r d e d O s s i f i c a t i o n (2 bil) S u p e r n u m e r a r y (site 13 bil) NAD NAD R e t a r d e d O s s i f i c a t i o n (2 bil) NAD R e t a r d e d O s s i f i c a t i o n (2 bil) NAD NAD NAD S u p e r n u m e r a r y (site 13 bil) R e t a r d e d O s s i f i c a t i o n (2 bil) VR DV VR VR DV VR 648534 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 4.85 5.02 5.15 5.24 5.16 4.87 4.50 4.59 5.05 5.23 4.93 4.85 5.16 4.50 4.36 Skull Skull NAD NAD NAD Retarded NAD Retarded NAD NAD NAD NAD NAD NAD NAD NAD NAD Ossification Ossification (2bil) (2bil) VR VR 648539 1 2 3 4.09 4.35 4.50 Skull Vertebra NAD Retarded Ossification Retarded Ossification (cen thll) NAD (2bil) VR VR om pany S a n itized . D o e s not con tain T SC * ''U - 145- H-24768: Developmental Toxicity Study in Rats_____________________________________________ DuPont-6515 INDIVIDUAL FETAL WEIGHTS (grams) A N D A L T E R ATIONS G R O U P IV: 4 0 0 M G / K G / D A Y DAM NO./ FETUS NO. FETUS W T . S T R U C T U R E FINDING(S) CLASSIFICATION 648539 (Cont.) 4 4.42 5 4.37 6 4.40 7 4.34 8 4.24 9 4.22 10 4.61 11 4.69 12 4.78 13 4. 5 4 14 4.25 Vertebra Retarded Ossification (cen t h l O , 11) NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD VR 648540 1 2 3 4 5 6 7 8 9 4.20 4.66 4.29 4.86 4.34 4.30 4.52 4.52 4.65 Vertebra Skull Vertebra Vertebra Skull Vertebra Vertebra Skull Vertebra Vertebra Skull Vertebra Vertebra Retarded Ossification (cen thll) Retarded Ossification Retarded Ossification (cen thlO-13) Retarded Ossification (cen t h l l - 13) Retarded Ossification Retarded Ossification (cen thlO-12) Retarded Ossification (cen thll) Retarded Ossification Retarded Ossification (cen thlO-12) Retarded Ossification (cen t h l l - 1 3 ) Retarded Ossification Retarded Ossification (cen th7,10-12) Retarded Ossification (cen thll-13) (2bil) (2bil) (2bil) (2bil) VR VR VR VR VR VR VR VR VR VR VR VR VR Com pany Sanitized. D oes not contain TSCA CSt - 146- H-24768: Developmental Toxicity Study in Rats DuPont-6515 INDIVIDUAL FETAL WEIGHTS (grams) A N D ALTERATIONS GROUP IV: 400 MG/KG/DAY DAM NO./ FETUS NO. FETUS W T . STRUCTURE FINDING(S) CLASSIFICATION 648540 (Cont.) 10 4.87 11 4.74 12 13 648552 1 2 3 4 5 6 7 8 9 10 11 648555 1 2 3 4 5 6 7 8 9 10 11 12 4.88 4.65 4.49 5.22 5.16 4.99 4.78 5.06 4.41 5.42 5.07 5.20 5.17 4.82 5.36 4.62 5.02 5.07 4.84 5.15 5.40 5.03 5.03 4.65 4.87 Vertebra Kidney Vertebra Vertebra Kidney Vertebra Vertebra Kidney Rib Skull Kidney Vertebra Kidney Retarded Ossification (cen t h l l , 12) Small Papilla - Size 2 Retarded Ossification (cen thlO-13) Retarded Ossification (cen thlO-12) NAD (bil) VR VR VR VR NAD NAD NAD NAD Small Papilla - Size 2 NAD Retarded Ossification (cen thlO) NAD Retarded Ossification (cen thll) NAD NAD (It) VR VR VR S m a l l P a p i l l a - S i z e 2 (bil) Supernumerary (site I4bil) NAD R e t a r d e d O s s i f i c a t i o n i(6bil) S m a l l P a p i l l a - S i z e 2 (It) NAD NAD NAD Retarded Ossification (cen th9) NAD S m a l l P a p i l l a - S i z e 2 (rt) NAD VR DV VR VR VR VR C om p an y S a n itized . D o e s not co n tain TSCA CBI - 147- H-24768: Developmental Toxicity Study in Rats DuPont-6515 INDIVIDUAL FETAL WEIGHTS (grams) A N D ALTERATIONS GROUP IV: 400 MG/KG/DAY DAM NO./ F E T U S NO. FETUS WT . STRUC T U R E FINDING(S) CLASSIFICATION 6 4 8 5 5 5 (Cont .) 13 4.94 648556 1 2 3 4 5 6 7 8 9 10 11 12 13 4.69 4.82 4.52 4.83 4.64 4.51 5.02 4.55 4.81 4.97 4.73 3.67 4.12 648560 1 2 3 4 5.17 5.04 4.88 4.74 5 4.71 6 4.93 7 4.49 8 4.52 9 5.12 10 5.46 11 4.99 12 4.75 13 4.87 Kidney Skull Skull Skull Skull Skull Vertebra Kidney Skull Rib Vertebra Vertebra Vertebra S m a l l P a p i l l a - S i z e 2 (It) VR NAD Retarded Ossification NAD Retarded Ossification NAD Retarded Ossification NAD NAD NAD Retarded Ossification NAD Retarded Ossification NAD (2bil) (2bil) (2bil) (2bil) (2 b i l ) VR VR VR VR VR NAD NAD NAD Retarded Ossification (cen t h l l , 12) NAD NAD P a p i l l a - S i z e 3 (rt) R e t a r d e d O s s i f i c a t i o n (2bil) NAD Supernumerary (site 14bil) Retarded Ossification (cen t h l O , 11) Retarded Ossification (cen thll) Retarded Ossification (cen th4) VR VR VR DV VR VR VR 648563 1 4.15 NAD Company S a n itized . D o e s not con tain TSCA CBI -148- H-24768: Developmental Toxicity Study in Rats DuPont-6515 INDIVIDUAL FETAL WEIGHTS (grams) A N D A L TERATIONS GROUP IV: 400 MG/KG/DAY DAM NO./ FETUS NO. FETUS WT . STRUCTURE FINDING(S) CLASSIFICATION 648563 (Cont.) 2 4.65 3 4.42 4 4.56 5 6 7 8 9 10 11 12 648570 1 2 3.89 4.77 4.47 4.56 4.25 4.38 4.97 5.30 4.72 4.85 3 4.87 4 4.42 5 4.90 6 4.80 7 5.09 8 5.16 9 4.86 10 4.79 11 4.73 12 4.19 13 4.61 Skull Vertebra Skull Vertebra Skull Rib Skull Sternebra Kidney Skull Vertebra Vertebra Kidney Kidney Vertebra Vertebra Kidney Vertebra Skull R e t a r d e d O s s i f i c a t i o n (2bil) Retarded Ossification (cen thl) R e t a r d e d O s s i f i c a t i o n (2bil) Retarded Ossification (cen thl2) NAD NAD NAD Retarded Ossification (2bil) Supernumerary (site 14bil) R e t a r d e d O s s i f i c a t i o n (2bil) NAD M i s a l i g n e d (4) VR VR VR VR VR DV VR DV S m a l l P a p i l l a - S i z e 2 (bil) R e t a r d e d O s s i f i c a t i o n (2bil) Retarded Ossification (cen t h l l , 12) NAD Retarded Ossification (cen thl2) S m a l l P a p i l l a - S i z e 2 (rt) P a p i l l a - S i z e 3 (It) Retarded Ossification (cen thll) Retarded Ossification (cen t h l l , 12) NAD P a p i l l a - S i z e 3 (rt) Retarded Ossification (cen thl0-13) NAD R e t a r d e d O s s i f i c a t i o n (2bil) NAD VR VR VR VR VR VR VR VR VR VR VR |& !n p a n x S a n itized . D o e s not con tain TSCA CB1 -149- H-24768: Developmental Toxicity Study in Rats DuPont-6515 INDIVIDUAL FETAL WEIGHTS (grams) AN D ALTERATIONS GROUP IV: 400 MG/KG/DAY DAM NO./ FETUS NO. FETUS WT. STRUCTURE FINDING(S) CLASSIFICATION 648577 1 2 3 4 5 6 7 8 9 10 11 12 13 14 648579 1 2 3 4 5 6 7 8 9 10 11 12 13 14 648583 1 2 3 5.22 4.93 4.61 4.56 4.95 4.49 4.93 5.26 4.67 4.85 4.69 4.52 4.64 4.66 Kidney Sternebra Sternebra Rib Vertebra 4.87 5.18 4.85 5.03 5.44 5.32 5.07 4.87 5.15 5.23 5.39 5.21 4.91 4.66 Sternebra Rib Rib Rib Rib Rib Rib 4.72 4.83 4.78 Vertebra P a p i l l a - S i z e 3 (It) NAD NAD R e t a r d e d O s s i f i c a t i o n (6) R e t a r d e d O s s i f i c a t i o n (6) Supernumerary (site 14rt) Retarded Ossification (cen thll) NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD NAD R e t a r d e d O s s i f i c a t i o n (6) NAD Supernumerary (site 14bil) NAD Supernumerary (site 14bil) Supernumerary (short 14bil) Supernumerary (site 141t) Supernumerary (site 14rt) Supernumerary (site 14bil) NAD NAD NAD Retarded Ossification (cen thll) NAD VR VR VR DV VR VR DV DV DV DV DV DV VR C o m p aq Sanitized. D o e s not contain TSCA CBI -150- H-24768: Developmental Toxicity Study in Rats DuPont-6515 INDIVIDUAL FETAL WEIGHTS (grams) AN D ALTERATIONS GROUP IV: 400 MG/KG/DAY DAM NO./ FETUS NO. FETUS WT . STRUCTURE F I N D I N G (S) CLASSIFICATION 648583 4 5 6 7 8 9 10 (Cont.) 4.57 4.38 4.49 4.67 4.86 4.57 4.73 648584 1 2 4.32 4.39 3 5.14 4 4.61 5 5.45 6 4.36 7 4.59 8 4.94 9 4.17 10 5.01 11 4.81 12 4.53 13 4 . 6 7 14 4.76 Skull Spleen Skull Rib Vertebra Kidney Rib Vertebra Rib Skull Subcutis Rib Vertebra Sternebra Rib NAD NAD Retarded Ossification Pale NAD NAD Retarded Ossification (2bil) (6rt) VR N VR Supernumerary (site 14bil) Retarded Ossification (cen thlO) S m a l l P a p i l l a - S i z e 2 (It) Supernumerary (site 14bil) NAD Retarded Ossification (cen thll) Supernumerary (site 14rt) R e t a r d e d Oss i f i c a t i o n (2bil) Hemorrhage (chest*) Supernumerary (short 14rt;site 14lt) Retarded Ossification (cen t h l l , 12) M i s a l i g n e d (3,4) Supernumerary (site 14bil) NAD NAD DV VR VR DV VR DV VR N DV VR DV DV 648586 1 2 3 4 5.79 5.61 5.35 5.78 Rib Sternebra Vertebra Sternebra Rib NAD Supernumerary (site 14bil) M i s a l i g n e d (3,4) Retarded Ossification (cen t h l l - 1 3 ) M i s a l i g n e d (4) Supernumerary (site 14bil) DV DV VR DV DV Company Sanitized. D oes not contain TSCA C si -151 - H-24768: Developmental Toxicity Study in Rats DuPont-6515 INDIVIDUAL FETAL WEIGHTS (grams) A N D A L T ERATIONS GROUP IV: 400 MG/KG/DAY DAM NO./ FETUS NO. FETUS W T . STRUCTURE FINDING(S) CLASSIFICATION 648586 5 6 (Cont.) 5.41 5.42 7 5.11 8 5.75 9 5.32 10 11 12 13 648589 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 648590 1 2 5.71 5.52 5.46 5.54 5.17 4.95 5.03 5.35 5.25 5.50 4.75 4.92 4.62 4.64 4.64 4.43 4.52 4.47 4.50 4.72 4.76 3 4.86 Rib Vertebra KidneyVertebra Vertebra Rib Rib Rib Skull Vertebra Supernumerary (site 141t) Retarded Ossification (cen thl2) NAD NAD P a p i l l a - S i z e 3 (rt) Retarded Ossification (cen thll) NAD Retarded Ossification (cen thl2) NAD Supernumerary (site 141t) DV VR VR VR VR DV NAD NAD NAD NAD NAD Supernumerary NAD NAD NAD NAD NAD NAD NAD NAD NAD (site 14rt) DV Supernumerary (site 14bil) R e t a r d e d O s s i f i c a t i o n (2bil) Retarded Ossification (cen thll) NAD DV VR VR -152- C om pany S an itized . D o e s not con tain TSCA CB1 H-24768: Developmental Toxicity Study in Rats DuPont-6515 INDIVIDUAL FETAL WEIGHTS (grams) A N D ALTERATIONS GROUP IV: 400 MG/KG/DAY DAM NO./ FETUS NO. FETUS W T . STRUCTURE FINDING(S) CLASSIFICATION 648590 (Cont.) 4 4.88 5 5.19 6 4.73 7 5.03 8 5.09 9 5.21 10 5.00 11 4.69 12 4.72 13 5.00 14 4.79 648597 1 2 4.94 4.07 3 4.76 4 4.72 5 4.74 6 5.60 7 4.25 8 5.47 9 5.53 10 5.01 11 4.82 12 5.04 Vertebra KidneyRib Rib Rib Rib Skull Vertebra Rib Skull Retarded Ossification (cen t h l l , 12) P a p i l l a - S i z e 3 (rt) Supernumerary (site 141t) NAD Supernumerary (site 141t) NAD NAD Supernumerary (site 14rt) NAD NAD Supernumerary (site 14bil) VR VR DV DV DV DV NAD Retarded Ossification Retarded Ossification (cen thll) NAD NAD Wavy (6-10rt) NAD NAD NAD NAD NAD NAD Retarded Ossification (2bil) (2bil) VR VR VR VR Com pany Sanitized. D oes not contain TSCA c a t H-24768: Developmental Toxicity Study in Rats DuPont-6515 APPENDIX H Analytical Report C o m p a n y S a n itized . D o e s not con tain t s c a CBI - 154- H-24768: Developmental Toxicity Study in Rats DuPont-6515 A. SAMPLE SUBMITTAL All dosing solution samples were collected on the same day the solutions were prepared for the study. The solution vehicle was deionized water. B. METHODS 1. Analytical Methods a. Dosing Solution Treatment Samples containing H-24768 at the concentrations o f 0, 5, 10, and 40 mg/mL were collected on May 4, 2001 for uniformity/concentration verification and 5-hour room temperature stability. Samples at the same concentrations were collected on May 11, 2001 and May 22, 2001 for concentration verification analysis Each dosing sample, prior to analysis, was diluted with methanol (0.5 mL) and an amount o f diluted control (to 0.5 mL total volume) to an expected concentration o f 2.5 or 4.0 mg/mL (a.i.). Samples submitted for analysis were analyzed the day the solutions were received by the testing group. b. Chromatographic Conditions Instrument: Column: Injector: Detector: Carrier Gas: Split vent: Injection Volume: Oven Program: Initial Temperature: Initial Time Level 1 Rate: Level 1 Temperature: Run Time: Hewlett-Packard Model 6890 GC HP-1, 30 m x 0.32 mm ID, 0.25 pm film thickness Split, 250C FID;300C Helium (2.6 mL/min) 52.9 mL/min 1 microliter Gradient 50C 0.0 min. 40C/min. 300C 22.25 minutes Company Sanitized. D o e s not con tain t s c a c m - 155 - H-24768: Developmental Toxicity Study in Rats DuPont-6515 c. Calibration and Quantitation A stock solution of the test material (a separate sample o f H-24768 used as analytical reference) was made in methanol. Before analysis of the samples in the study, appropriate aliquots o f the stock were diluted with the methanol after an equivalent amount o f the diluted control to match the samples was added. These solutions were used to make calibration standards that bracketed the target concentration o f the diluted dosing samples. Peak heights (4 retention times) from GC analysis of these standards were used to construct calibration curves by least square regression (see Figure la - Id for a representative calibration curves). Measured concentrations for dosing solutions were determined by applying the peak heights from replicate injections o f the samples to each calibration curve. The mean result from the concentrations at all retention times (n = 4) is reported as the concentration for the sample. Test substance uniformity in the vehicle was evaluated by calculating the coefficient o f variation (C.V. = standard deviation/mean x 100) of the measured concentrations in duplicate samples for each dosing level. A coefficient o f variation o f less than 10% is the standard criterion at Haskell Laboratory for acceptable distribution o f the test substance throughout the solution. The mean result of the duplicate samples for each dosing level was used to determine the concentration o f the test substance for the respective dosing levels. Stability was evaluated by using the mean of the duplicate samples for concentration verification as the baseline for comparing the corresponding room temperature results. C. ANALYTICAL RESULTS 1. Chromatography H-24768 eluted from the GC column as resolved peaks over retention time range of approximately 5 to 20 minutes. For the purpose o f quantitation, the retention times o f approximately 7.9, 8.2, 8.5, and 9.0 minutes were determined to be representative o f the test substance in the dosing matrix. Representative GC chromatograms are shown in Figures 2(a - cj. Test substance was not detected in the 0 mg/mL control. .Com pany S a n itized . D o e s Wot con tain TSCA CBl -156- H-24768: Developmental Toxicity Study in Rats DuPont-6515 2. Concentration Verification and Stability Samples Analytical results from dosing solutions prepared May 4, 2001, and analyzed for concentration verification and stability are shown in Table I and Summary Table 1. The following table summarizes the results for uniformity/concentration verification and stability analyses for this preparation. Preparation Date 4-May-2001 Nominal mg/mL 5.0 10.0 40.0 Measured8 Average CV Stability0 mg/mL % Nominal % % Nominal 4.72, 4.66 93.8 1 91.6 8.90, 8.80 88.5 1 89.5 37.2, 38.2 94.3 2 92.0 a Duplicate samples analyzed. b Stabilitysamples held for5 hours atroom temperature. The results for samples prepared on May 4, 2001, show that the test substance was adequately mixed (CV's = 1 , 1 and 2), at the targeted levels (target = 11.5% o f nominal) and stable ( 10.5% o f nominal) in the vehicle when held 5 hours at room temperature. Test substance was not detected in the 0 mg/mL sample. The following ta b li^ n m a r iz e ^ g s u lt^ jr stability samples from a previous developmental toxicity pilot s t u d y S ^ f H ^ ^ ^ B f These results indicate that the test substance in the vehicle was stable w ten held 4-days refrigerated followed by 5 hours at room temperature and support the stability o f the test substance under the conditions o f this study. Preparation Nominal Date mg/mL Measured8 Average CV Stability1* Stability0 mg/mL % Nominal % % Nominal % Nominal 7-Mar-01 5.0 4.72,4.54 92.6 10.0 9.36, 8.75 90.5 40.0 40.2, 38.9 98.9 70.0 63.2,61.7 89.1 3 101.2 107.4 5 97.0 97.2 ? 105.2 103.3 2 120.3 99.6 a Duplicate samples analyzed, b Stabilitysamples held for4 days refrigerated. c Stabilitysamples held for4 days refrigerated, then 5 hours atroom temperature. pm pany S an itized . Does not contain TSCA CB* - 157- H-24768: Developmental Toxicity Study in Rats DuPont-6515 3. Concentration Verification Samples Analytical results from dosing solutions prepared May 11, 2001 and May 22, 2001 and analyzed for concentration verification are shown in Table II and Summary Table 1. The following table summarizes the results for concentration verification analyses for the preparations. Preparation Date 11-May-2001 Nominal mg/mL 5.0 10.0 40.0 Measured3 mg/mL 5.06, 5.03 9.62,10.07 42.0, 40.6 Average % Nominal 101.0 98.5 103.3 CV % 0.4 3 2 22-May-2001 5.0 10.0 40.0 4.73,5.01 9.22, 9.65 37.3, 36.5b 97.4 4 94.4 1 92.3 2 a Duplicate samples per level were analyzed. C.V. calculated to verify uniformity of mixture, b Mean result of the original analysis and duplicate reanalysis of the original sample reported. The results for these samples indicate that the test substance was adequately mixed (CV's less than 10) and at the targeted levels (target = 8.7% o f nominal) for all samples. Test substance was not detected in the 0 mg/mL sample. 4. Conclusions Results from the analysis of the samples during the study indicate that the test substance was mixed properly, at the targeted levels and stable under the conditions o f the study. Test substance was not found in the 0 mg/mL samples. Com pany Sanitized. D oes not contain tsca cut -158- H-24768: Developmental Toxicity Study in Rats ANALYTICAL SUMMARY TABLE 1 DuPont-6515 SUMMARY OF DOSING SOLUTION ANALYSES Sample Type ________________Dosing Concentrations and Stability o f H-24768(mg/mL) 4-May-2001 Concentration Verification Nominal: Average M easured Cone.*3 Average Percent Nominal*3 Standard Deviation*3 Coefficient of Variation*3 5.00 4.72 (94.4)a 4.66 (93.2) 4.69 (93.8) 0.1 1% 10.0 8.90 (89.0) 8.80 (88.0) 8.85 (88.5) 0.1 1% 40.0 37.2 (93.0) 38.2 (95.5) 37.7 (94.3) 0.7 2% Stabilitv 4.58c (91.6) 8.95c (89.5) 36.8e (92.0) Concentration Verification4* 11-May-2001 5.05 (101.0) 9.85 (98.5) 41.3 (103.3) 22-May-2001 4.87 (97.4) 9.44 (94.4) 36.9e (92.3) Nominal: Concentration Verification^ Average M easured Cone.*3 Average Percent Nominal*3 Standard Deviation*3 Coefficient of Variation*3 5.00 4.72 (94.4) 4.54 (90.8) 4.63 (92.6) 0.1 3% 10.00 9.36 (93.6) 8.75 (87.5) 9.05 (90.5) 0.4 5% 40.00 40.2 (100.5) 38.9 (97.3) 39.6 (98.9) 0.9 2% Stabilitv 5.06S (101.2) 9.70S (97.0) 42.1S (105.2) 5.37h (107.4) 9.72h (97.2) 41..3*1 (103.3) a Numbers in parentheses are the respective percent of nominal values. b Mean, S.D. and C.V. for duplicate samples calculated to verify uniformity of mixture, c Samples held at room temperature for 5 hours, d Duplicate samples submitted. Mean result reported, e Mean result of all analyses, f Samples from previous study for Work Request 1 g Samples held refrigerated for 4 days and sample^ b Samples held refrigerated for 4 days followed by 5 hours at room temperature. 70.00 63.2 (90.2) 61.7 (88.1) 62.4 (89.1) 1.1 2% 84.2g (120.3) 69.7h (99.6) C om pa/iy S an itized . D o e s not con tain TSGA CB* - 159- H-24768: Developmental Toxicity Study in Rats Analytical Table I. Concentration Verification and Stability ofH-24768 inDosing Solutions Preparation Date ___________ mg/mL H-24768___________ Percent ______ Sample Type____________Nominal__________ Measured__________ Nominal 4-May-2001 Concentration Verification^) Control 0.0 n d (B) -- 5.0- 1 5.0- 2 Mean: 4.72 4,66 4.69 0.1 C.V. 1% 94.4 93.2 (93.8) 10.0-1 10.0-2 Mean: 8.90 8.80 8.85 0.1 C.V. 1% 89.0 88.0 (88.5) 40.0- 1 40.0- 2 Mean: 37.2 38.2 37.7 0.7 C.V. 2% 93.0 95.5 (94.3) Stability 5-Hour Room Temperature 5.0 4.58 91.6 5-Hour Room Temperature 10.0 8.95 89.5 5-Hour Room Temperature 40.0 36.8 (A) Duplicate samples per level were analyzed. Mean, S.D. and C.V. calculated to verily uniformity of mixture. (B) Denotes not detected. 92.0 DuPont-6515 Company Sanitized. Does not contain TSCA CBl - 160- H-24768: Developmental Toxicity Study in Rats Analytical Table I. (continued) Concentration Verification and Stability of H-24768 in Dosing Solutions Preparation Date mg/mL H-24768 Percent Sample Type Nominal Measured Nominal 7-Mar-2001 Concentration Verification^) Control 0.0 n d (b ) -- 5.0-1 5.0-2 Mean: 4.72 4.54 4.630.1 C.V. 3% 94.4 90.8 (92.6) 10.0-1 10.0-2 Mean: 9.36 8.75 9.050.4 C.V. 5% 93.6 87.5 (90.5) 40.0-1 40.0-2 Mean: 40.2 38.9 39.60.9 C.V.2% 100.5 97.3 (98.9) 70.0-1 70.0-2 Mean: 63.2 61.7 62.4L1 C.V.2% 90.2 88.1 (89.1) Stability 4-Day Refrigerated 5 Hour Room Tem perature^) 5.0 5.0 5.06 101.2 5.37 107.4 4-Day Refrigerated 5 Hour Room Temperature(C) 10.0 10.0 9.70 9.72 97.0 97.2 4-Day Refrigerated 40.0 42.1 105.2 5 Hour Room Temperature'C) 40.0 41.3 103.3 4-Day Refrigerated 7 5 Hour Room Tem perature^)________ \ 120.3 99.6 (A) Duplicate samples from Work Request No. fere analyzed. Table included for reference. Mean, S.D. y uniformity o f mixture. (B) Denotes not detected. (C) Samples held for 4 days refrigerated, then 5 hours at room temperature. DuPont-6515 Company Sanitized. D o es not contain TSCA o w - 161 - H-24768: Developmental Toxicity Study in Rats DuPont-6515 Analytical Table II. Concentration Verification of H-24768 in Dosing Solutions Preparation Date Sample Type 11-May-2001 mg/mL H-24768 Nominal Measured Concentration Verification(^) Control 0.0 n d (b ) 5.0-1 5.0-2 Mean: 5.06 5.03 5.05 0.02 C.V. 0.4% 10.0-1 10.0-2 Mean: 9.62 10.07 9.85 0.3 C.V.3% 40.0-1 40.0-2 Mean: 42.0 40.6 41.3 0.99 C.V. 2% Percent Nominal -- 101.2 100.6 (101.0) 96.2 100.7 (98.5) 105.0 101.5 (103.3) 22-May-2001 Concentration Verific a tio n i) Control 0.0 n d (b ) -- 5.0-1 5.0-2 Mean: 4.73 5.01 4.87 0.2 C.V. 4% 94.6 100.2 (97.4) 10.0-1 10.0-2 Mean: 9.22 9.65 9.44 0.3 C.V. 3% 92.2 96.5 (94.4) 40.0-1 37.3 93.3 40.0-2 40.0-2A 40.0-2B mean^C); Mean: 34.3 38.7 36.4 36.5 36.9 0.6 C.V.2% 85.8 96.8 91.0 91.3 (92.3) (A) Duplicate samples per level were analyzed. Mean, S.D. and C. V. calculated to verify uniformity o f mixture. (B) Denotes not detected. (C) Mean result reported for the original analysis o f Sample 2 (-2) and duplicate aliquots o f the original sample (-2A, -2B). This mean result was used as the concentration for Sample 2 and average with Sample 1 for the reported concentration o f the 40 mg/mL sample. - 162- C om pany S an itized . Does no! contain TSOA H-24768: Developmental Toxicity Study in Rats Figure 1 Representative Analytical Calibration Curve DuPont-6515 Figure la: Calibration curve (R.T. = 7.9 minutes) showing linear fit(line) to replicate peak height measurements (squares) for calibration solutions of H-24768 diluted over a concentration range of 1.56 to 6.49 mg/mL. Concentration, mg/mL Figure lb: Calibration curve (R.T. = 8.2 minutes) showing linear fit(line) to replicate peak height measurements (squares) for calibration solutions of H-24768 diluted over a concentration range of 1.56 to 6.49 mg/mL. C om p an y S a n itized . D o e s not con tain TSCA CBI -163 - H-24768: Developmental Toxicity Study in Rats Figure 1 (continued) Representative Analytical Calibration Curve DuPont-6515 Figure lc: Calibration curve (R.T. = 8.5 minutes) showing linear fit(line) to replicate peak height measurements (squares) for calibration solutions of H-24768 diluted over a concentration range of 1.56 to 6.49 mg/mL. Concentration, mg/mL Figure Id: Calibration curve (R.T. = 8.9-9.0 minutes) showing linear fit(line) to replicate peak height measurements (squares) for calibration solutions of H-24768 diluted over a concentration range of 1.56 to 6.49 mg/mL. G&mpanx Sanitized. D oes not contain TSCA CM - 164- H-24768: Developmental Toxicity Study in Rats Figure 2 Representative Gas Chromatography Chromatograms DuPont-6515 Figure 2a: Representative G C chromatogram of 0 mg/mL (control) sample. Retention times used for H-24768 are approximately 7.9, 8.2, 8.5, and 9.0 minutes. Figure 2b: Representative G C chromatogram of40.0 mg/mL H-24768 dosing solution diluted to a nominal concentration of 4.00 mg/mL. The measured concentration of the representative solution is42.0 mg/mL. Figure 2c: Representative G C chromatogram of 3.25 mg/mL H-24768 analytical reference solution. -165- Sginpaftjr Santteecl. Does not contain TSCA CBt